A Phase 1 Study to Evaluate MEDI6383 Alone and in Combination with MEDI4736 in Adult Subjects with Select Advanced Solid Tumors

Study identifier:D6050C00001

ClinicalTrials.gov identifier:NCT02221960

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI6383 Alone and in Combination with MEDI4736 in Adult Subjects with Select Advanced Solid Tumors

Medical condition

Recurrent or metastatic solid tumors

Phase

Phase 1

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 15 Sept 2014

Primary Completion Date: 03 Jul 2017

Study Completion Date: 03 Jul 2017

Study design

Allocation: Non-randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2018 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1.)Male and female subjects; age ≥ 18
2.)Written informed consent must be obtained
3.)Subjects must meet the following criteria:
a.Have recurrent or metastatic solid tumors
b.Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Subjects should not have received more than 5 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies
4.)Subjects must have at least 1 lesion
5.)Subjects must consent to provide archived tumor specimens and / or tumor biopsy for correlative biomarker studies.
6.)Eastern Cooperative Oncology Group performance score of 0 or 1
7.)In the opinion of the invesgator likely to complete ≥ 8 weeks of treatment.
8.)Adequate organ function as determined by:
i. Absolute neutrophil count ≥ 1.5 x 109/L (1,500/mm3)
ii.Platelet count ≥ 100 x 109/L (100,000/mm3)
iii.Hemoglobin ≥ 9.0 g/dL within first 2 weeks prior to first dose of investigational product
iv.Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50 mL/min
v.Total bilirubin ≤ 1.5× ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 3× ULN
vi.Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5× ULN
vii.Serum Electrolytes within normal limits
9.)Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of highly effective contraception from screening, and must agree to continue using such precautions for 90 days after the final dose of investigational product;
10) Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 through 90 days after receipt of the final dose of investigational product

Exclusion Criteria

1.)Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR) .
2.)Subjects who have received prior therapy with regimens containing CTLA-4, PDL-1, or PD-1 antagonists are NOT permitted to enroll unless all of the following apply:
◦ Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
◦ All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or baseline prior to screening for this study.
3.) Must not have experienced a ≥ Grade 3 AE or neurologic or ocular AE of any grade while receiving prior immunotherapy
4.)History of severe allergic reactions to any unknown allergens or any components of the study drug formulations
5.)Active or prior documented autoimmune disease within the past 2 years.
6.)Untreated central nervous system metastatic disease l
7.)Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study
8.)Receipt of anticancer therapy within 28 days prior to the first dose of Investigational Product
9.)Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
10.)Unresolved toxicities from prior anticancer therapy
11.)Systemic anticoagulation or daily aspirin dose exceeding 325 mg per day
12.)Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI6383. )
13.) History of primary immunodeficiency, solid organ transplantation, or tuberculosis
14.)True positive test results for human immunodeficiency virus (HIV) or hepatitis B or C
15.)Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products )
16.)Pregnant or breastfeeding women
17.)Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI6383 or still recovering from prior surgery. Local surgery of isolated lesions for palliative intent is acceptable
18.)Other invasive malignancy within 2 years
-

Location

Research Site

Nashville, TN, United States, 37203

Location

Research Site

Portland, OR, United States, 97213

Location

Research Site

Chicago, IL, United States, 60611

Location

Research Site

La Jolla, CA, United States, 92093

Location

Research Site

New Haven, CT, United States, 06520

Location

Research Site

New York, NY, United States, 10065

Location

Research Site

Washington, DC, United States, 20007

Location

Research Site

Parkville, Australia, 3052

Arms	Assigned Interventions
Experimental: Monotherapy Arm MEDI6383	Biological/Vaccine: MEDI6383 Subjects will receive MEDI6383 until disease progression or adverse event.
Experimental: Combination Arm MEDI6383 and MEDI4736	Biological/Vaccine: MEDI6383 and MEDI4736 Subjects will recieve MEDI6383 and MEDI4736 until disease progression or adverse event.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted from 15Sep2014 to 03Jul2017 in the United States of America and Australia. A total of 52 participants were screened for enrollment in the study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 52 participants, 39 were enrolled and treated with at least 1 dose of study drug in dose-escalation phase. Enrollment was discontinued during dose-escalation phase due to strategic decision at sponsor’s discretion, not related to safety of either MEDI6383 monotherapy or combination of MEDI6383 with MEDI4736 (durvalumab).

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Participant Flow: Overall Study

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
STARTED	3	3	3	4	5	3	4	3	6	5
COMPLETED	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	3	3	3	4	5	3	4	3	6	5
Death	3	2	2	4	3	2	2	2	2	3
Lost to Follow-up	0	0	0	0	1	0	0	0	1	0
Unspecified	0	1	0	0	0	0	2	0	0	1
Withdrawal by Subject	0	0	1	0	1	1	0	1	3	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Baseline Measures

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10	Total
Number of Participants [units: Participants]	3	3	3	4	5	3	4	3	6	5	39
Age Continuous [units: Years] Mean ± Standard Deviation	60.7 ± 10.8	64.3 ± 11.5	74.0 ± 6.2	55.3 ± 10.5	50.2 ± 18.7	65.7 ± 8.1	57.3 ± 9.4	57.7 ± 3.2	54.8 ± 16.4	50.2 ± 14.1	57.6 ± 13.2
Sex: Female, Male [units: ]
Female	0	0	0	1	4	1	3	1	3	2	15
Male	3	3	3	3	1	2	1	2	3	3	24
Race/Ethnicity, Customized [units: Participants]
Hispanic Or Latino	0	1	0	0	0	0	0	0	0	1	2
Not Hispanic Or Latino	3	2	3	3	5	3	4	3	6	4	36
Missing	0	0	0	1	0	0	0	0	0	0	1
Race/Ethnicity, Customized [units: Participants]
American Indian or Alaskan Native	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0	0	0	0
Black Or African American	0	1	0	1	0	0	0	0	0	1	3
Native Hawaiian Or Other Pacific Islander	0	0	0	1	0	0	0	0	0	0	1
White	3	2	3	2	5	3	4	2	6	4	34
Other	0	0	0	0	0	0	0	1	0	0	1

Outcome Measures

1. Primary Outcome Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: From the start of study drug administration (Day 1) up to 12 weeks after the last study dose (up to 3 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Measure Description	An adverse event is any unfavourable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with use of medicinal product, whether or not considered related to medicinal product. Serious adverse event is any AE that resulted in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug and up to 12 weeks post end of treatment (up to 3 years).
Time Frame	From the start of study drug administration (Day 1) up to 12 weeks after the last study dose (up to 3 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [units: Participants]
TEAEs	3	3	3	4	5	3	4	3	6	5
TESAEs	2	0	2	1	3	1	2	1	2	2

No statistical analysis provided for Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

2. Primary Outcome Measure: Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: From the start of study drug administration (Day 1) to Day 28 ]

Measure Type	Primary
Measure Name	Number of Participants With Dose-limiting Toxicities (DLTs)
Measure Description	A DLT was defined as any Grade 3 or higher toxicity that occurred during the DLT-evaluation period. DLT-evaluation period, defined as the time period from the first dose of study drug through 28 days post dose.
Time Frame	From the start of study drug administration (Day 1) to Day 28
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
DLT-evaluable population included all participants enrolled in the dose-escalation phase who received 2 doses of assigned study drug per protocol during the first 28 days and completed the safety follow-up through the DLT-evaluation period (time period from the first dose of study drug through 28 days post dose) or experience any DLT.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Number of Participants With Dose-limiting Toxicities (DLTs) [units: Participants]	0	0	0	0	0	0	0	0	1	0

No statistical analysis provided for Number of Participants With Dose-limiting Toxicities (DLTs)

3. Primary Outcome Measure: Maximum tolerated dose of MEDI6383 [ Time Frame: From the start of study drug administration (Day 1) up to 12 weeks post end of treatment (up to 3 years) ]

Measure Type	Primary
Measure Name	Maximum tolerated dose of MEDI6383
Measure Description	Study was terminated due to a strategic decision at the sponsor’s discretion. No participants were analyzed for this outcome measure.
Time Frame	From the start of study drug administration (Day 1) up to 12 weeks post end of treatment (up to 3 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	0	0	0	0	0	0	0	0	0	0
Maximum tolerated dose of MEDI6383 [units: Participants]

No statistical analysis provided for Maximum tolerated dose of MEDI6383

4. Primary Outcome Measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs [ Time Frame: From the start of study drug administration (Day 1) up to 12 weeks post end of treatment (up to 3 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Measure Description	An abnormal laboratory finding which required an action or medical intervention by the investigator, or a finding judged by the investigator as medically significant should be reported as an adverse event. Laboratory evaluation (haematology, serum chemistry, and urinalysis) of blood and urine were performed.
Time Frame	From the start of study drug administration (Day 1) up to 12 weeks post end of treatment (up to 3 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs [units: Participants]
Anaemia	1	1	0	0	1	0	1	1	1	1
Lymphopenia	0	1	0	0	0	0	0	0	1	0
Neutropenia	0	0	0	0	0	0	0	0	1	1
Thrombocytopenia	0	0	0	0	0	0	0	0	2	0
Platelet count decreased	0	1	0	0	0	0	0	0	0	0
Alanine aminotransferase increased	0	0	0	1	0	0	0	0	3	0
Amylase increased	0	0	0	0	0	0	0	1	1	1
Aspartate aminotransferase increased	0	1	0	1	0	0	0	0	3	0
Blood albumin increased	0	1	0	0	0	0	0	0	0	0
Blood alkaline phosphatase increased	0	1	0	1	0	0	0	1	2	0
Blood bilirubin increased	0	1	0	0	0	0	0	0	1	0
Blood creatinine increased	0	0	1	0	0	0	0	1	1	0
Gamma-glutamyltransferase increased	0	1	0	0	0	0	0	0	0	0
Lipase increased	0	0	0	0	0	0	0	1	1	0
Hypercalcemia	1	0	0	0	0	0	0	0	0	0
Hyperglycemia	0	1	0	1	0	0	0	0	0	0
Hyperkalemia	0	0	0	1	0	0	0	0	0	0
Hypoalbuminemia	0	0	0	1	0	0	0	0	1	0
Hypocalcemia	0	0	0	1	0	0	0	0	0	0
Hypokalemia	0	0	0	0	0	0	1	1	0	0
Hypomagnesemia	0	0	1	0	0	0	0	0	0	0
Hyponatremia	0	0	0	1	0	0	0	0	1	0
Hypophosphatemia	0	0	0	1	0	0	0	0	0	0
Hematuria	0	0	0	0	0	0	0	1	0	0

No statistical analysis provided for Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs

5. Primary Outcome Measure: Number of Participants With Vital Signs Abnormalities Reported as TEAEs [ Time Frame: From the start of study drug administration (Day 1) up to 12 weeks post end of treatment (up to 3 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Vital Signs Abnormalities Reported as TEAEs
Measure Description	Vital sign parameters included blood pressure, temperature, pulse rate, and respiratory rate. TEAEs observed in participants with clinically significant vital signs abnormalities were reported.
Time Frame	From the start of study drug administration (Day 1) up to 12 weeks post end of treatment (up to 3 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Number of Participants With Vital Signs Abnormalities Reported as TEAEs [units: Participants]
Hypotension	1	0	0	0	0	0	0	0	0	0
Sinus tachycardia	1	0	0	0	0	0	0	0	0	0
Weight decreased	1	0	0	0	0	0	0	1	0	0
Atrial fibrillation	0	0	0	1	0	0	0	0	0	0
Tachycardia	0	0	0	0	1	0	1	0	0	0
Hypoxia	0	0	0	0	1	0	1	0	0	0
Hypertension	0	0	0	0	0	1	0	0	0	0
Pyrexia	0	0	0	0	0	0	0	1	0	2

No statistical analysis provided for Number of Participants With Vital Signs Abnormalities Reported as TEAEs

6. Primary Outcome Measure: Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs [ Time Frame: From the start of study drug administration (Day 1) up to 12 weeks post end of treatment (up to 3 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs
Measure Description	TEAEs observed in participants with clinically significant ECG abnormalities were reported.
Time Frame	From the start of study drug administration (Day 1) up to 12 weeks post end of treatment (up to 3 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs [units: Participants]
Sinus tachycardia	1	0	0	0	0	0	0	0	0	0
Atrial fibrillation	0	0	0	1	0	0	1	0	0	0
Tachycardia	0	0	0	0	1	0	1	0	0	0

No statistical analysis provided for Number of Participants With Electrocardiogram Abnormalities Reported as TEAEs

7. Secondary Outcome Measure: Percentage of Participants With Objective Response [ Time Frame: From study entry until disease progression, or death, or end of study (up to 3 years) ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Objective Response
Measure Description	The objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1). Complete Response (CR) is evaluated as the disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm (the sum may not be “0” if there are target nodes). Partial response (PR) was evaluated as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	From study entry until disease progression, or death, or end of study (up to 3 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Percentage of Participants With Objective Response [units: Percentage of participants] Number (95% Confidence Interval)	0 (0.0 to 70.8)	0 (0.0 to 70.8)	0 (0.0 to 70.8)	0 (0.0 to 60.2)	0 (0.0 to 52.2)	0 (0.0 to 70.8)	0 (0.0 to 60.2)	0 (0.0 to 70.8)	0 (0.0 to 45.9)	20.0 (0.5 to 71.6)

No statistical analysis provided for Percentage of Participants With Objective Response

8. Secondary Outcome Measure: Percentage of Participants With Disease Control [ Time Frame: From study entry until disease progression, or death, or end of study (up to 3 years) ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Disease Control
Measure Description	Disease control is defined as CR, PR, or stable disease (SD); participants achieving SD were to be included in the disease control rate if they maintain SD for ≥8 or 24 weeks (±3 days) from start of treatment. The disease control rate at 8/24 weeks (DCR 8/24) is defined as the proportion of subjects with a best overall response (BOR) of CR, PR, or SD maintained for ≥8 or 24 weeks. DCR8 and DCR24 were reported.
Time Frame	From study entry until disease progression, or death, or end of study (up to 3 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Percentage of Participants With Disease Control [units: Percentage of participants] Number (95% Confidence Interval)
Disease control rate at 8 weeks	33.3 (0.8 to 90.6)	0 (0.0 to 70.8)	66.7 (9.4 to 99.2)	0 (0.0 to 60.2)	0 (0.0 to 52.2)	0 (0.0 to 70.8)	0 (0.0 to 60.2)	33.3 (0.8 to 90.6)	0 (0.0 to 45.9)	40.0 (5.3 to 85.3)
Disease control rate at 24 weeks	0 (0.0 to 70.8)	0 (0.0 to 70.8)	0 (0.0 to 70.8)	0 (0.0 to 60.2)	0 (0.0 to 52.2)	0 (0.0 to 70.8)	0 (0.0 to 60.2)	0 (0.0 to 70.8)	0 (0.0 to 45.9)	20.0 (0.5 to 71.6)

No statistical analysis provided for Percentage of Participants With Disease Control

9. Secondary Outcome Measure: Duration of Response (DR) [ Time Frame: From study entry until disease progression, or death, or end of study (up to 3 years) ]

Measure Type	Secondary
Measure Name	Duration of Response (DR)
Measure Description	Duration of response is defined as the duration from the first documentation of objective response (CR and PR) to the first documented disease progression or death due to any cause, whichever occurs first.
Time Frame	From study entry until disease progression, or death, or end of study (up to 3 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug. Participants who achieved CR and PR were analyzed.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	0	0	0	0	0	0	0	0	0	1
Duration of Response (DR) [units: Months] Median (95% Confidence Interval)										10.8 (10.8 to 10.8)

No statistical analysis provided for Duration of Response (DR)

10. Secondary Outcome Measure: Progression-free Survival (PFS) [ Time Frame: From study entry until disease progression, or death, or end of study (up to 3 years) ]

Measure Type	Secondary
Measure Name	Progression-free Survival (PFS)
Measure Description	Progression-free survival was measured from the start of treatment with study drug until the first documentation of disease progression or death due to any cause, whichever occurred first.
Time Frame	From study entry until disease progression, or death, or end of study (up to 3 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Progression-free Survival (PFS) [units: Months] Median (Full Range)	3.4 (1.8 to 5.1)	1.8 (1.7 to 1.9)	7.4 (1.9 to 9.2)	1.9 (1.8 to 1.9)	1.8 (0.7 to 5.5)	1.3 (1.0 to 1.7)	1.9 (1.8 to 3.6)	1.7 (1.7 to 3.8)	1.6 (1.2 to 1.8)	3.7 (1.8 to 12.5)

No statistical analysis provided for Progression-free Survival (PFS)

11. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: From study entry until disease progression, or death, or end of study (up to 3 years) ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	Overall survival was determined as the time from the start of treatment with study drug until death due to any cause.
Time Frame	From study entry until disease progression, or death, or end of study (up to 3 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Overall Survival (OS) [units: Months] Median (Full Range)	5.1 (1.4 to 6.5)	9.1 (1.8 to 13.2)	19.0 (5.2 to 19.0)	13.9 (0.9 to 17.8)	8.9 (0.6 to 17.3)	3.5 (1.1 to 5.0)	8.2 (2.0 to 17.2)	4.6 (3.7 to 24.4)	15.7 (2.3 to 15.7)	15.5 (1.9 to 17.5)

No statistical analysis provided for Overall Survival (OS)

12. Secondary Outcome Measure: Maximum observed serum concentration (Cmax) of MEDI6383 [ Time Frame: Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]). ]

Measure Type	Secondary
Measure Name	Maximum observed serum concentration (Cmax) of MEDI6383
Measure Description	The maximum observed serum concentration of MEDI6383.
Time Frame	Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Maximum observed serum concentration (Cmax) of MEDI6383 [units: mcg/mL] Mean (Standard Deviation)	0.157 (0.0632)	0.620 (0.348)	2.79 (0.629)	8.05 (6.60)	42.5 (13.5)	170 (38.2)	574 (84.5)	0.587 (0.197)	0.873 (0.457)	2.25 (0.436)

No statistical analysis provided for Maximum observed serum concentration (Cmax) of MEDI6383

13. Secondary Outcome Measure: Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI6383 [ Time Frame: Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]). ]

Measure Type	Secondary
Measure Name	Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI6383
Measure Description	The area under the concentration time curve from time 0 to time of the last quantifiable concentration of MEDI6383.
Time Frame	Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI6383 [units: day*mcg/ mL] Mean (Standard Deviation)	0.0247 (0.0107)	0.240 (0.219)	1.38 (0.769)	3.66 (3.11)	9.36 (3.99)	39.2 (7.13)	314 (130)	0.243 (0.122)	0.454 (0.420)	1.05 (0.433)

No statistical analysis provided for Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI6383

14. Secondary Outcome Measure: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC 0-infinity) of MEDI6383 [ Time Frame: Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]). ]

Measure Type	Secondary
Measure Name	Area Under the Concentration-time Curve From Time 0 to Infinity (AUC 0-infinity) of MEDI6383
Measure Description	The area under the concentration-time curve from time 0 to infinity of MEDI6383.
Time Frame	Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC 0-infinity) of MEDI6383 [units: day*mcg/ mL] Mean (Standard Deviation)	NA (NA)^[1]	0.347 (0.202)	1.50 (0.899)	3.86 (3.31)	9.44 (4.01)	39.3 (7.01)	314 (130)	0.268 (0.126)	0.539 (0.560)	1.12 (0.500)

No statistical analysis provided for Area Under the Concentration-time Curve From Time 0 to Infinity (AUC 0-infinity) of MEDI6383

15. Secondary Outcome Measure: Systemic Clearance (CL) of MEDI6383 [ Time Frame: Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]). ]

Measure Type	Secondary
Measure Name	Systemic Clearance (CL) of MEDI6383
Measure Description	The systemic clearance of MEDI6383 was evaluated.
Time Frame	Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Systemic Clearance (CL) of MEDI6383 [units: Liters/day] Mean (Standard Deviation)	NA (NA)^[1]	25.8 (15.6)	23.6 (11.9)	38.9 (31.7)	28.5 (11.9)	20.6 (5.18)	11.0 (4.65)	17.6 (15.5)	30.3 (17.6)	27.4 (14.7)

No statistical analysis provided for Systemic Clearance (CL) of MEDI6383

16. Secondary Outcome Measure: Terminal Elimination Half-life (t½) of MEDI6383 [ Time Frame: Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]). ]

Measure Type	Secondary
Measure Name	Terminal Elimination Half-life (t½) of MEDI6383
Measure Description	Terminal phase elimination half-life of MEDI6383.
Time Frame	Cycle 1 (Day 1 [predose; 10 min, 2 and 6 hours postdose], Days 2, 3, 8, and Day 15 [predose]).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Terminal Elimination Half-life (t½) of MEDI6383 [units: Day] Mean (Standard Deviation)	NA (NA)^[1]	0.309 (0.0706)	0.489 (0.0633)	0.649 (0.344)	1.19 (0.118)	1.12 (0.318)	1.88 (0.668)	0.365 (0.0971)	0.457 (0.283)	0.460 (0.104)

No statistical analysis provided for Terminal Elimination Half-life (t½) of MEDI6383

17. Secondary Outcome Measure: Number of Participants With Positive Anti-Drug Antibodies to MEDI6383 [ Time Frame: Day 1 (predose), Days 15, 29, 43, 57, 71, 85, 99, 113, every 2 weeks until EOT (14 days after last dose of study drug), EOT, and 30 days post EOT (up to 3 years). ]

Measure Type	Secondary
Measure Name	Number of Participants With Positive Anti-Drug Antibodies to MEDI6383
Measure Description	The number of participants with positive anti-drug antibodies to MEDI6383 were presented.
Time Frame	Day 1 (predose), Days 15, 29, 43, 57, 71, 85, 99, 113, every 2 weeks until EOT (14 days after last dose of study drug), EOT, and 30 days post EOT (up to 3 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Number of Participants With Positive Anti-Drug Antibodies to MEDI6383 [units: Participants]
ADA positive at baseline	0	0	0	0	0	0	0	0	0	0
ADA positive post-baseline	0	2	2	1	0	2	1	1	1	2

No statistical analysis provided for Number of Participants With Positive Anti-Drug Antibodies to MEDI6383

18. Secondary Outcome Measure: Number of Participants With Positive Anti-Drug Antibodies to MEDI4736 [ Time Frame: Day 1 (Predose), Days 29, 57, 85, 113, and 12 weeks post EOT (up to 3 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With Positive Anti-Drug Antibodies to MEDI4736
Measure Description	The number of participants with positive anti-drug antibodies to MMEDI4736 were presented.
Time Frame	Day 1 (Predose), Days 29, 57, 85, 113, and 12 weeks post EOT (up to 3 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	6	5
Number of Participants With Positive Anti-Drug Antibodies to MEDI4736 [units: Participants]
ADA positive at baseline	0	0	0
ADA positive post-baseline	0	0	0

No statistical analysis provided for Number of Participants With Positive Anti-Drug Antibodies to MEDI4736

19. Secondary Outcome Measure: Induction of Ki67 on Peripheral CD4+ Memory T Cells [ Time Frame: From screening up to 12 weeks post end of treatment (up to 3 years). ]

Measure Type	Secondary
Measure Name	Induction of Ki67 on Peripheral CD4+ Memory T Cells
Measure Description	The induction of Ki67 on peripheral CD4 memory T-cell populations were presented.
Time Frame	From screening up to 12 weeks post end of treatment (up to 3 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Induction of Ki67 on Peripheral CD4+ Memory T Cells [units: Percentage] Mean (Standard Deviation)
Nominal time= 0 (baseline)	0.505 (0.361)	5.02 (3.26)	7.28 (3.13)	7.84 (2.78)	2.23 (1.35)	3.80 (0.509)	3.62 (2.39)	3.83 (2.76)	3.20 (1.24)	4.55 (4.11)
Nominal time= 1	0.850 (NA)^[1]	6.58 (2.83)	4.38 (2.01)	7.29 (6.05)	2.27 (0.422)	3.19 (2.31)	2.88 (2.16)	4.49 (3.19)	2.23 (0.668)	5.58 (4.79)
Nominal time= 14	0.960 (0.0990)	5.03 (3.07)	6.12 (6.92)	7.08 (5.23)	1.72 (NA)^[1]	2.19 (0.778)	5.35 (0.877)	6.95 (3.71)	2.25 (1.18)	4.67 (2.87)
Nominal time= 28	1.77 (1.15)	4.25 (2.87)	5.30 (1.79)	5.31 (5.26)	1.28 (NA)^[1]	3.17 (1.61)	6.73 (1.56)	4.95 (0.608)	3.56 (1.44)	5.54 (2.18)
Nominal time= 84	3.00 (1.77)		2.49 (2.50)	1.51 (NA)^[1]	4.21 (NA)^[1]		3.82 (NA)^[1]	3.35 (1.15)		3.05 (0.431)

No statistical analysis provided for Induction of Ki67 on Peripheral CD4+ Memory T Cells

20. Secondary Outcome Measure: Induction of Ki67 on Peripheral CD8+ Memory T Cells [ Time Frame: From screening up to 12 weeks post end of treatment (up to 3 years). ]

Measure Type	Secondary
Measure Name	Induction of Ki67 on Peripheral CD8+ Memory T Cells
Measure Description	The induction of Ki67 on peripheral CD8 memory T-cell populations were presented.
Time Frame	From screening up to 12 weeks post end of treatment (up to 3 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The As-treated population included participants who received any study drug.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Measured Values

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10
Number of Participants Analyzed [units:participants]	3	3	3	4	5	3	4	3	6	5
Induction of Ki67 on Peripheral CD8+ Memory T Cells [units: Percentage] Mean (Standard Deviation)
Nominal time= 0 (baseline)	0.450 (0.481)	5.70 (3.40)	6.69 (2.40)	6.98 (5.47)	1.98 (1.42)	2.51 (0.728)	5.39 (3.32)	4.50 (3.86)	2.32 (0.905)	4.08 (4.52)
Nominal time= 1	0.790 (NA)^[1]	7.70 (3.24)	3.33 (1.66)	7.84 (6.91)	2.44 (1.41)	1.95 (1.33)	2.40 (2.46)	4.01 (2.80)	2.04 (1.23)	4.25 (3.90)
Nominal time= 14	2.66 (2.24)	4.31 (3.91)	4.42 (2.55)	8.83 (8.03)	1.35 (NA)^[1]	1.92 (0.649)	2.60 (0.785)	6.11 (1.78)	3.07 (0.576)	6.15 (5.82)
Nominal time= 28	2.23 (2.04)	3.91 (2.61)	5.92 (0.962)	3.44 (3.50)	1.82 (NA)^[1]	2.22 (0.358)	5.77 (3.91)	4.58 (3.17)	2.88 (0.882)	8.34 (4.48)
Nominal time= 84	2.07 (0.735)		1.74 (1.51)	1.14 (NA)^[1]	1.80 (NA)^[1]		2.64 (NA)^[1]	4.03 (2.65)		2.75 (0.509)

No statistical analysis provided for Induction of Ki67 on Peripheral CD8+ Memory T Cells

Serious Adverse Events

Time Frame	From the start of study drug administration (Day 1) up to 12 weeks after the last dose of study drug (up to 3 years).
Additional Description	No text entered.

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Serious Adverse Events

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Cohort 6

Cohort 7

Cohort 8

Cohort 9

Cohort 10

Total, serious adverse events

# participants affected / at risk

2/3 (66.67%)

0/3 (0.00%)

2/3 (66.67%)

1/4 (25.00%)

3/5 (60.00%)

1/3 (33.33%)

2/4 (50.00%)

1/3 (33.33%)

2/6 (33.33%)

2/5 (40.00%)

Cardiac disorders

Arrhythmia supraventricular¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Pericardial effusion¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Stress cardiomyopathy¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

2/6 (33.33%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Enterocutaneous fistula¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Small intestinal obstruction¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Pelvic infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cell carcinoma¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of lung¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Cauda equina syndrome¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchial secretion retention¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 20.0

Other Adverse Events

Time Frame	From the start of study drug administration (Day 1) up to 12 weeks after the last dose of study drug (up to 3 years).
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Cohort 1	Participants received an intravenous (IV) infusion dose of MEDI6383 0.05 milligram per kilogram (mg/kg) every two weeks (Q2W).
Cohort 2	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg Q2W.
Cohort 3	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg Q2W.
Cohort 4	Participants received an IV infusion dose of MEDI6383 1.0 mg/kg Q2W.
Cohort 5	Participants received an IV infusion dose of MEDI6383 3.0 mg/kg Q2W.
Cohort 6	Participants received an IV infusion dose of MEDI6383 10 mg/kg Q2W.
Cohort 7	Participants received an IV infusion dose of MEDI6383 30 mg/kg Q2W.
Cohort 8	Participants received an IV infusion dose of MEDI6383 0.05 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 9	Participants received an IV infusion dose of MEDI6383 0.1 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.
Cohort 10	Participants received an IV infusion dose of MEDI6383 0.3 mg/kg in combination with a single dose level of MEDI4736 10 mg/kg Q2W.

Other Adverse Events

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Cohort 6

Cohort 7

Cohort 8

Cohort 9

Cohort 10

Total, other (not including serious) adverse events

# participants affected / at risk

3/3 (100.00%)

4/4 (100.00%)

4/5 (80.00%)

3/3 (100.00%)

4/4 (100.00%)

3/3 (100.00%)

6/6 (100.00%)

5/5 (100.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

1/4 (25.00%)

1/3 (33.33%)

1/6 (16.67%)

1/5 (20.00%)

# events

Blood and lymphatic system disorders

Lymphopenia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

1/5 (20.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

2/6 (33.33%)

0/5 (0.00%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Pericardial effusion¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Sinus tachycardia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Cardiac disorders

Tachycardia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Ear and labyrinth disorders

Tinnitus¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Endocrine disorders

Hypothyroidism¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Astigmatism¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Dry eye¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Ocular hyperaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Photopsia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Eye disorders

Ulcerative keratitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Eye disorders

Vitreous floaters¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal discomfort¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

1/3 (33.33%)

1/4 (25.00%)

2/3 (66.67%)

2/6 (33.33%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Abdominal pain lower¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Autoimmune colitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

1/3 (33.33%)

2/3 (66.67%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

2/3 (66.67%)

2/6 (33.33%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/3 (33.33%)

1/4 (25.00%)

2/5 (40.00%)

0/3 (0.00%)

1/4 (25.00%)

2/3 (66.67%)

3/6 (50.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Dry mouth¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Faeces discoloured¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Flatulence¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Haemorrhoidal haemorrhage¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

1/4 (25.00%)

1/5 (20.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

2/6 (33.33%)

2/5 (40.00%)

# events

Gastrointestinal disorders

Rectal discharge¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

2/5 (40.00%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Axillary pain¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Catheter site swelling¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Chills¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

1/3 (33.33%)

2/3 (66.67%)

1/3 (33.33%)

2/4 (50.00%)

2/5 (40.00%)

2/3 (66.67%)

2/4 (50.00%)

1/3 (33.33%)

4/6 (66.67%)

4/5 (80.00%)

# events

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Medical device pain¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

1/5 (20.00%)

# events

General disorders and administration site conditions

Pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Performance status decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

2/5 (40.00%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Hordeolum¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Oropharyngeal candidiasis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Pelvic abscess¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Infections and infestations

Skin infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Contusion¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Excoriation¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Infusion related reaction¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

3/6 (50.00%)

1/5 (20.00%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

3/6 (50.00%)

0/5 (0.00%)

# events

Investigations

Amylase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

1/5 (20.00%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

3/6 (50.00%)

0/5 (0.00%)

# events

Investigations

Blood albumin increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Investigations

Blood alkaline phosphatase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

2/6 (33.33%)

0/5 (0.00%)

# events

Investigations

Blood bilirubin increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

0/5 (0.00%)

# events

Investigations

Blood thyroid stimulating hormone increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Investigations

Ejection fraction decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Investigations

Gamma-glutamyltransferase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Investigations

Lipase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

0/5 (0.00%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Acidosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

1/3 (33.33%)

2/3 (66.67%)

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

2/3 (66.67%)

0/4 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypercalcaemia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypoalbuminaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypocalcaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypophosphataemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

2/5 (40.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

2/5 (40.00%)

# events

Musculoskeletal and connective tissue disorders

Fistula¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Flank pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Limb discomfort¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

0/3 (0.00%)

2/4 (50.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

2/5 (40.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Musculoskeletal and connective tissue disorders

Pathological fracture¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acrochordon¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Cognitive disorder¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

2/6 (33.33%)

0/5 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/3 (0.00%)

2/3 (66.67%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

1/5 (20.00%)

# events

Nervous system disorders

Horner's syndrome¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Nervous system disorders

Neuropathy peripheral¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Nervous system disorders

Piriformis syndrome¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Visual field defect¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Psychiatric disorders

Mental status changes¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Chromaturia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Reproductive system and breast disorders

Breast swelling¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Erectile dysfunction¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Oedema genital¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Reproductive system and breast disorders

Pelvic pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

1/4 (25.00%)

1/3 (33.33%)

0/6 (0.00%)

2/5 (40.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

2/5 (40.00%)

1/3 (33.33%)

1/4 (25.00%)

1/3 (33.33%)

0/6 (0.00%)

2/5 (40.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Paranasal sinus hypersecretion¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Sinus congestion¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

1/6 (16.67%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Upper-airway cough syndrome¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Wheezing¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Onychoclasis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/6 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus generalised¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

2/3 (66.67%)

0/6 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

2/6 (33.33%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹,^†

# participants affected / at risk

0/3 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

2/5 (40.00%)

# events

Skin and subcutaneous tissue disorders

Rash pruritic¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Skin mass¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

1/4 (25.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Urticaria¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Flushing¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/5 (20.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

1/3 (33.33%)

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Vascular disorders

Subclavian artery stenosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 20.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Shaad Abdullah
Organization:	MedImmune, LLC
Phone	+1 301-398-4330
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Medimmune Medimmune

Medimmune, LLC

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Trial Results Summaries