Safety and Tolerability of Pembrolizumab (MK-3475) + Pegylated Interferon Alfa-2b and Pembrolizumab+ Ipilimumab in Participants With Advanced Melanoma or Renal Cell Carcinoma (MK-3475-029/KEYNOTE-29)

• ClinicalTrials.gov Identifier: NCT02089685
• Recruitment Status: Completed
• First Posted: March 18, 2014
• Results First Posted: May 18, 2022
• Last Update Posted: September 13, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Renal Cell Carcinoma; Melanoma
• Interventions: Biological: Pembrolizumab; Biological: PegIFN-2b; Biological: Ipilimumab
• Enrollment: 295

Participant Flow

Recruitment Details
Pre-assignment Details	Per protocol, response or progression during the second course were not counted towards efficacy outcome measure and adverse events during the second course were not counted towards safety outcome measures. Part 2 of the study was not conducted.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + Pegylated Interferon Alfa-2b (PEG-IFN) 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab + IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description	Participants in Part 1A received pembrolizumab intravenously (IV) 200 mg every 3 weeks (Q3W) for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg subcutaneously (SC) once a week for up to ~2 years. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg every 6 weeks (Q6W) for up to ~24 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg every 12 weeks (Q12W) for up to 48 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.
Period Title: Overall Study
Started	23	14	3	153	51	51
Treated	22	14	3	153	51	51
Completed	0	0	0	0	0	0
Not Completed	23	14	3	153	51	51
Reason Not Completed
Adverse Event	1	0	0	0	1	0
Clinical Progression	4	0	0	5	1	2
Excluded Medication	1	0	0	11	2	1
Progressive disease	13	10	3	51	17	12
Follow up ended by sponsor	2	2	0	70	26	26
Withdrawal by Subject	0	2	0	8	1	1
Status not recorded	1	0	0	0	1	0
Death	0	0	0	7	2	5
Lost to Follow-up	0	0	0	1	0	0
Physician Decision	0	0	0	0	0	4
Screen failure	1	0	0	0	0	0

Baseline Characteristics

Arm/Group Title		Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + Pegylated Interferon Alfa-2b (PEG-IFN) 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab + IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg	Total
Arm/Group Description		Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to 48 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.	Total of all reporting groups
Overall Number of Baseline Participants		23	14	3	153	51	51	295
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	23 participants	14 participants	3 participants	153 participants	51 participants	51 participants	295 participants
		59.4 (12.3)	60.3 (10.4)	61.7 (18.5)	59.9 (12.5)	60.8 (12.9)	62.8 (11)	60.5 (12.2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	14 participants	3 participants	153 participants	51 participants	51 participants	295 participants
	Female	10 43.5%	5 35.7%	0 0.0%	52 34.0%	13 25.5%	18 35.3%	98 33.2%
	Male	13 56.5%	9 64.3%	3 100.0%	101 66.0%	38 74.5%	33 64.7%	197 66.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	14 participants	3 participants	153 participants	51 participants	51 participants	295 participants
	Hispanic or Latino	1 4.3%	0 0.0%	0 0.0%	1 0.7%	2 3.9%	0 0.0%	4 1.4%
	Not Hispanic or Latino	21 91.3%	9 64.3%	2 66.7%	142 92.8%	41 80.4%	45 88.2%	260 88.1%
	Unknown or Not Reported	1 4.3%	5 35.7%	1 33.3%	10 6.5%	8 15.7%	6 11.8%	31 10.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	14 participants	3 participants	153 participants	51 participants	51 participants	295 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	2 8.7%	0 0.0%	0 0.0%	1 0.7%	1 2.0%	1 2.0%	5 1.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	1 7.1%	1 33.3%	0 0.0%	0 0.0%	0 0.0%	2 0.7%
	White	19 82.6%	13 92.9%	1 33.3%	150 98.0%	42 82.4%	46 90.2%	271 91.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%	2 1.3%	0 0.0%	0 0.0%	2 0.7%
	Unknown or Not Reported	2 8.7%	0 0.0%	1 33.3%	0 0.0%	8 15.7%	4 7.8%	15 5.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Dose-limiting Toxicities (DLTs) (Part 1A)
Description	Participants in Part 1A were analyzed for DLTs. DLTs included all adverse experiences that were clearly not related to disease progression or intercurrent illness if judged by the investigator to be possibly, probably, or definitely related to study intervention. Reported adverse experiences used the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.0. DLTs were analyzed and reported separately for protocol specified clinical indications of metastatic melanoma (MEL) and renal cell carcinoma (RCC) in Part 1A: Part 1A Pembrolizumab + IPI 1mg/kg (MEL), Part 1A Pembrolizumab + IPI 1 mg/kg (RCC), Part 1A Pembrolizumab + PEG-IFN 1 µg/kg (MEL), Part 1A Pembrolizumab + PEG-IFN 1 µg/kg (RCC), Part 1A Pembrolizumab + PEG-IFN 2 µg/kg (RCC). Per protocol, DLT outcome analysis did not include Parts 1B and 1C.
Time Frame	Up to ~6 Weeks

Outcome Measure Data

Analysis Population Description

Participants in Part 1A with MEL and RCC who completed the first cycle of study treatment or discontinued from trial due to drug-related adverse event (DRAE). DLTs were analyzed and reported separately for protocol specified clinical indications of MEL and RCC in Part 1A. Per protocol, Parts 1B and 1C were excluded from DLT outcome analysis.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg (MEL)	Part 1A Pembrolizumab + IPI 1 mg/kg (RCC)	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg (MEL)	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg (RCC)	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg (RCC)	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A with MEL received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A with RCC received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A with MEL received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A with RCC received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A with RCC received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	11	8	5	9	3	0	0	0
Measure Type: Number; Number (80% Confidence Interval); Unit of Measure: Percentage of Participants
	36.4; (20.6 to 54.5)	25; (10.2 to 45.4)	20; (5.1 to 44.8)	0.0; (0.0 to 14.9)	66.7; (36.5 to 89.4)

2. Primary Outcome

Title	Percentage of Participants Experiencing Adverse Events (AEs)
Description	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0.The number of participants who experienced at least one AE was reported.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study treatment.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	22	14	3	153	51	51
Measure Type: Number; Unit of Measure: Percentage of Participants
	100.0	100.0	100.0	99.3	100.0	100.0

3. Primary Outcome

Title	Percentage of Participants Discontinuing Study Drug Due to AEs
Description	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Reported adverse experiences used the CTCAE Version 4.0. The percentage of participants who discontinued study treatment due to an AE was reported.
Time Frame	Up to ~24 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study treatment.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	22	14	3	153	51	51
Measure Type: Number; Unit of Measure: Percentage of Participants
	40.9	50.0	66.7	37.3	19.6	37.3

4. Primary Outcome

Title	Percentage of Participants Experiencing Adverse Events of Special Interest (AEOSIs) (Parts 1B and 1C)
Description	AEOSIs consist of immune-mediated events, infusion reactions and depression. Events include Pneumonitis, Colitis, Hepatitis, Nephritis, Adrenal Insufficiency, Hypophysitis, Hyperthyroidism, Hypothyroidism, Thyroiditis, Type 1 Diabetes Mellitus, Skin Disorders, Uveitis, Pancreatitis, Myositis, Guillain-Barre Syndrome, Myocarditis, Encephalitis, Sarcoidosis, Infusion Reactions, Myasthenic Syndrome, Myelitis, Vasculitis, and Cholangitis Sclerosing. Per protocol Part 1B and Part 1C are reported. Part 1A was not included in the AEOIs outcome analysis, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All randomized participants in Part 1B and Part 1C who received at least one dose of study treatment. Part 1A was not included in the AEOIs outcome analysis, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	153	51	51
Measure Type: Number; Unit of Measure: Percentage of Participants
				60.8	45.1	56.9

5. Primary Outcome

Title	Percentage of Participants Experiencing Grade 3-5 Drug-related AEs (Part 1C)
Description	Participants in Part 1C who experienced grade 3-5 drug-related AEs (DRAEs) using CTCAE Version 4.0 are presented. Grade 3-5 DRAEs for Parts 1A and 1B was a secondary outcome analysis, per protocol and reported later in the record.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All randomized participants in Part 1C who received at least one dose of study treatment. Grade 3-5 DRAEs in Parts 1A and 1B were reported separately as a secondary outcome analysis, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	0	51	51
Measure Type: Number; Unit of Measure: Percentage of Participants
					27.5	43.1

6. Primary Outcome

Title	Objective Response Rate (ORR) (Part 1C)
Description	ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The percentage of participants who experienced a CR or PR is presented. Per protocol, ORR in Part 1C was planned and conducted as a pre-specified primary outcome analysis. ORR in Part 1B was planned and conducted as a protocol-specified secondary outcome analysis and has been reported later in the record. Outcome analysis of ORR in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

Participants in Part 1C with measurable disease at baseline based on central independent review, who had ORR data available. Per protocol, ORR in Part 1C was planned and conducted as a pre-specified primary outcome analysis. ORR in Part 1B was planned and conducted as a protocol-specified secondary outcome analysis and has been reported later in the record. Outcome analysis of ORR in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	0	46	43
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
					69.6; (54.2 to 82.3)	76.7; (61.4 to 88.2)

7. Primary Outcome

Title	Progression-free Survival (PFS) (Part 2)
Description	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS was to be assessed by independent central review per RECIST 1.1. Part 2 of the study was not conducted, based on protocol specified criteria and this Part 2 specific outcome measure could not be reported.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

Part 2 of the study was not conducted, based on protocol specified criteria and this Part 2 specific outcome measure could not be reported.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Secondary Outcome

Title	Objective Response Rate (ORR) (Part 1B)
Description	ORR was defined as the percentage of participants who had a CR: Disappearance of all target lesions or a PR: At least a 30% decrease in the sum of diameters of target lesions as assessed using RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. Per protocol, ORR in Part 1B was planned and conducted as a pre-specified secondary outcome analysis. ORR in Part 1C was planned and conducted as a protocol-specified primary outcome analysis and has been reported earlier in the record. Outcome analysis of ORR in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

Participants in Part 1B with measurable disease at baseline based on central independent review, who had ORR data available. Per protocol, ORR in Part 1B was planned and conducted as a pre-specified secondary outcome analysis. ORR in Part 1C was planned and conducted as a protocol-specified primary outcome analysis and has been reported earlier in the record. Outcome analysis of ORR in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	146	0	0
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
				65.8; (57.5 to 73.4)

9. Secondary Outcome

Title	ORR by Programmed-death Receptor-ligand 1 (PD-L1) Status Using RECIST 1.1 (Parts 1B and 1C)
Description	ORR was defined as the percentage of participants who had a CR: Disappearance of all target lesions or a PR: At least a 30% decrease in the sum of diameters of target lesions as assessed using RECIST 1.1. The percentage of participants that experienced a CR or PR by PD-L1 status is presented. PD-L1 positivity was defined as ≥1% staining in tumor and inflammatory cells, while PD-L1 negativity is defined as <1% staining. ORR for participants in Parts 1B and 1C with measurable disease at baseline based on central independent review, who had ORR data available for PD-L1+ and PD-L1- participants are presented. Outcome analysis of ORR in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

Participants in Parts 1B and 1C with measurable disease at baseline based on central independent review, who had ORR data available for PD-L1+ and PD-L1- participants. Outcome analysis of ORR in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title		Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:		Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed		0	0	0	144	41	38
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
PD-L1 Positive	Number Analyzed	0 participants	0 participants	0 participants	121 participants	28 participants	27 participants
					67.8; (58.7 to 76.0)	75.0; (55.1 to 89.3)	85.2; (66.3 to 95.8)
PD-L1 Negative	Number Analyzed	0 participants	0 participants	0 participants	23 participants	13 participants	11 participants
					52.2; (30.6 to 73.2)	53.8; (25.1 to 80.8)	63.6; (30.8 to 89.1)

10. Secondary Outcome

Title	Percentage of Participants With an Ordinal Response, Estimated by a Best Overall Response of VGPR or MPR (Parts 1B and 1C)
Description	Ordinal response, per RECIST 1.1 included the best overall responses of Very Good Partial Response ([VGPR]>60% tumor reduction) as well as Moderate Partial Response ([MPR]>30%- ≤60% tumor reduction). The percentage of participants in Part 1B and 1C who experienced a MPR or VGPR (based on the degree of tumor shrinkage) in participants with advanced melanoma is presented. Outcome analysis of ordinal response in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All randomized participants in Part 1B and Part 1C who received at least one dose of study treatment and had data available for VGPR or MPR. Outcome analysis of ordinal response in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	146	46	43
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
MPR				6.2; (2.9 to 11.4)	8.7; (2.4 to 20.8)	23.3; (11.8 to 38.6)
VGPR				24.0; (17.3 to 31.7)	28.3; (16.0 to 43.5)	20.9; (10.0 to 36.0)

11. Secondary Outcome

Title	Duration of Response (DOR) (Parts 1B and 1C)
Description	DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on central imaging review with confirmation. The DOR as assessed using RECIST 1.1 for participants with measurable disease at baseline based on central independent review in Parts 1B and 1C who experienced a confirmed CR or PR with DOR data available is presented. Outcome analysis of DOR in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

Participants in Parts 1B and 1C with measurable disease at baseline based on central independent review, who had a confirmed CR or PR, with DOR data available. Outcome analysis of DOR in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	96	32	33
Median (Full Range); Unit of Measure: Months
				NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [2]; (3.8 to NA)

[1]

Median and range lower and upper limit not reached. No progressive disease by the time of last disease assessment.

[2]

Median and range upper limit not reached. No progressive disease by the time of last disease assessment.

12. Secondary Outcome

Title	Progression-free Survival (PFS) (Parts 1B and 1C)
Description	PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by independent central review per RECIST 1.1 for all participants who received at least one dose of study treatment in Part 1B and all randomized participants in Part 1C, who had PFS data available is presented. Outcome analysis of PFS in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment in Part 1B and all randomized participants in Part 1C, who had PFS data available. Outcome analysis of PFS in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	153	51	51
Median (95% Confidence Interval); Unit of Measure: Months
				NA [1]; (36.4 to NA)	NA [1]; (14.1 to NA)	NA [1]; (31.9 to NA)

[1]

Median and range upper limit of PFS was not reached. No progressive disease by the time of last disease assessment.

13. Secondary Outcome

Title	Overall Survival (OS) (Parts 1B and 1C)
Description	OS was defined as the time from randomization to death due to any cause. OS for all participants who received at least one dose of study treatment in Part 1B and all randomized participants in Part 1C, who had OS data available is presented. Outcome analysis of OS in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment in Part 1B and all randomized participants in Part 1C, who had OS data available. Outcome analysis of OS in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab + IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	153	51	51
Median (95% Confidence Interval); Unit of Measure: Months
				NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [2]; (39.6 to NA)

[1]

Median and range lower and upper limits not reached due to insufficient number of OS events.

[2]

Median and range upper limits not reached due to insufficient number of OS events.

14. Secondary Outcome

Title	PFS by PD-L1 Status Using RECIST 1.1 (Parts 1B and 1C)
Description	PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PD-L1 positivity was defined as ≥1% staining in tumor and inflammatory cells, while PD-L1 negativity is defined as <1% staining. PFS for all participants who received at least one dose of study treatment in Part 1B and all randomized participants in Part 1C, who had PFS data available for PD-L1+ and PD-L1- participants is presented. Outcome analysis of PFS in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment in Part 1B and all randomized participants in Part 1C, who had PFS data available for PD-L1+ and PD-L1- participants. Outcome analysis of PFS in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title		Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab + IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:		Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed		0	0	0	151	46	44
Median (95% Confidence Interval); Unit of Measure: Months
PD-L1 Positive	Number Analyzed	0 participants	0 participants	0 participants	127 participants	32 participants	31 participants
					NA [1]; (41.6 to NA)	NA [2]; (NA to NA)	NA [1]; (35.7 to NA)
PD-L1 Negative	Number Analyzed	0 participants	0 participants	0 participants	24 participants	14 participants	13 participants
					20.7 [3]; (2.8 to NA)	23.1 [3]; (1.4 to NA)	13.8 [3]; (1.4 to NA)

[1]

Median and range upper limit not reached. No progressive disease by the time of last disease assessment.

[2]

Median and range lower and upper limit not reached. No progressive disease by the time of last disease assessment.

[3]

Range upper limit not reached. No progressive disease by the time of last disease assessment.

15. Secondary Outcome

Title	OS by PD-L1 Status Using RECIST 1.1 (Parts 1B and 1C)
Description	OS was defined as the time from randomization to death due to any cause. PD-L1 positivity was defined as ≥1% staining in tumor and inflammatory cells, while PD-L1 negativity is defined as <1% staining. OS for all participants who received at least one dose of study treatment in Part 1B and all randomized participants in Part 1C, who had OS data available for PD-L1+ and PD-L1- participants is presented. Outcome analysis of OS in Part 1A was not planned or conducted in this study, per protocol.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment in Part 1B and all randomized participants in Part 1C, who had OS data available for PD-L1+ and PD-L1- participants. Outcome analysis of OS in Part 1A was not planned or conducted in this study, per protocol.

Arm/Group Title		Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab + IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:		Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed		0	0	0	151	46	44
Median (95% Confidence Interval); Unit of Measure: Months
PD-L1 Positive	Number Analyzed	0 participants	0 participants	0 participants	127 participants	32 participants	31 participants
					NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
PD-L1 Negative	Number Analyzed	0 participants	0 participants	0 participants	24 participants	14 participants	13 participants
					NA [1]; (14.1 to NA)	32.8 [1]; (12.9 to NA)	NA [1]; (7.6 to NA)

[1]

Median and range lower and upper limits not reached due to insufficient number of OS events.

16. Secondary Outcome

Title	Percentage of Participants Experiencing Grade 3-5 DRAEs (Parts 1A and 1B)
Description	Participants in Parts 1A and 1B who experienced DRAEs using CTCAE Version 4.0 are presented. Grade 3-5 DRAEs for Part 1C was a primary outcome analysis, per protocol and reported earlier in the record.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

All randomized participants in Parts 1A and 1B who received at least one dose of study treatment. Grade 3-5 DRAEs in Part 1C were reported separately as a primary outcome analysis, per protocol.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab + IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	22	14	3	153	0	0
Measure Type: Number; Unit of Measure: Percentage of Participants
	90.9	71.4	66.7	70.6

17. Secondary Outcome

Title	ORR (Part 2)
Description	ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. Part 2 of the study was not conducted, based on protocol specified criteria and this Part 2 specific outcome measure was not reported.
Time Frame	Up to ~84 months

Outcome Measure Data

Analysis Population Description

Part 2 of the study was not conducted, based on protocol specified criteria and this Part 2 specific outcome measure could not be reported.

Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg	Part 1A Pembrolizumab + PEG-IFN 1 µg/kg	Part 1A Pembrolizumab + PEG-IFN 2 µg/kg	Part 1B Pembrolizumab+ IPI 1 mg/kg	Part 1C Pembrolizumab + IPI 50 mg	Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description:	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years.	Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years.	Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks.	Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to ~48 weeks.
Overall Number of Participants Analyzed	0	0	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Up to approximately 84 months (through database cutoff date of 01-April-2021).
Adverse Event Reporting Description	All-cause mortality: All randomized participants. Safety: All randomized participants who received at least 1 dose of study treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Arm/Group Title	Part 1A Pembrolizumab + IPI 1 mg/kg		Part 1A Pembrolizumab + PEG-IFN 1 µg/kg		Part 1A Pembrolizumab + PEG-IFN 2 µg/kg		Part 1B Pembrolizumab + IPI 1 mg/kg		Part 1C Pembrolizumab + IPI 50 mg		Part 1C Pembrolizumab + IPI 100 mg
Arm/Group Description	Participants in Part 1A received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.		Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 1 µg/kg SC once a week for up to ~2 years. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year.		Participants in Part 1A received pembrolizumab IV 200 mg Q3W + PEG-IFN 2 µg/kg SC once a week for up to ~2 years. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year.		Participants in Part 1B received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 1 mg/kg Q3W for up to ~12 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.		Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 50 mg Q6W for up to ~24 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at the investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.		Participants in Part 1C received pembrolizumab IV 200 mg Q3W for up to ~2 years + IPI IV 100 mg Q12W for up to 48 weeks. Qualified participants who received the first course but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at the same dose and schedule for up to ~1 additional year + IPI at the same dose and schedule for up ~12 additional weeks.
All-Cause Mortality
	Part 1A Pembrolizumab + IPI 1 mg/kg		Part 1A Pembrolizumab + PEG-IFN 1 µg/kg		Part 1A Pembrolizumab + PEG-IFN 2 µg/kg		Part 1B Pembrolizumab + IPI 1 mg/kg		Part 1C Pembrolizumab + IPI 50 mg		Part 1C Pembrolizumab + IPI 100 mg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	16/23 (69.57%)		10/14 (71.43%)		2/3 (66.67%)		51/153 (33.33%)		14/51 (27.45%)		17/51 (33.33%)
Serious Adverse Events
	Part 1A Pembrolizumab + IPI 1 mg/kg		Part 1A Pembrolizumab + PEG-IFN 1 µg/kg		Part 1A Pembrolizumab + PEG-IFN 2 µg/kg		Part 1B Pembrolizumab + IPI 1 mg/kg		Part 1C Pembrolizumab + IPI 50 mg		Part 1C Pembrolizumab + IPI 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/22 (40.91%)		9/14 (64.29%)		2/3 (66.67%)		78/153 (50.98%)		26/51 (50.98%)		25/51 (49.02%)
Blood and lymphatic system disorders
Anaemia † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Cardiac disorders
Acute coronary syndrome † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Atrial fibrillation † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	3/153 (1.96%)	3	0/51 (0.00%)	0	0/51 (0.00%)	0
Atrioventricular block † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Autoimmune myocarditis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Coronary artery disease † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	1/51 (1.96%)	1	0/51 (0.00%)	0
Myocardial infarction † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	0/51 (0.00%)	0	0/51 (0.00%)	0
Sinus tachycardia † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Ear and labyrinth disorders
Deafness † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Deafness neurosensory † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Endocrine disorders
Adrenal insufficiency † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	1/51 (1.96%)	1	1/51 (1.96%)	1
Adrenocortical insufficiency acute † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Autoimmune thyroiditis † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Hyperthyroidism † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	3/153 (1.96%)	3	0/51 (0.00%)	0	0/51 (0.00%)	0
Hypophysitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	0/51 (0.00%)	0	1/51 (1.96%)	1
Hypopituitarism † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Lymphocytic hypophysitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Eye disorders
Necrotising scleritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	0/51 (0.00%)	0	1/51 (1.96%)	1
Abdominal pain upper † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Autoimmune colitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	3/153 (1.96%)	3	1/51 (1.96%)	1	1/51 (1.96%)	1
Autoimmune pancreatitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Colitis † 1	3/22 (13.64%)	3	0/14 (0.00%)	0	0/3 (0.00%)	0	6/153 (3.92%)	6	2/51 (3.92%)	3	2/51 (3.92%)	2
Constipation † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Diarrhoea † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	2/153 (1.31%)	2	0/51 (0.00%)	0	0/51 (0.00%)	0
Enteritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Gastric ulcer † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Gastritis erosive † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Inguinal hernia † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Intestinal obstruction † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Intestinal perforation † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Lower gastrointestinal haemorrhage † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Nausea † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Pancreatitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Pancreatitis acute † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	2
Rectal haemorrhage † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Small intestinal obstruction † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Vomiting † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
General disorders
Chest discomfort † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Chest pain † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Fatigue † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Influenza like illness † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	2/51 (3.92%)	2
Pyrexia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	1/51 (1.96%)	1	1/51 (1.96%)	1
Hepatobiliary disorders
Autoimmune hepatitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	8/153 (5.23%)	8	0/51 (0.00%)	0	0/51 (0.00%)	0
Bile duct stone † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Biliary obstruction † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	2	0/51 (0.00%)	0	0/51 (0.00%)	0
Cholecystitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	0/51 (0.00%)	0	0/51 (0.00%)	0
Cholecystitis acute † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Hepatic vascular thrombosis † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Immune system disorders
Cytokine release syndrome † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Hypersensitivity † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Infections and infestations
Bronchitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Bronchitis viral † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Bronchopulmonary aspergillosis allergic † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Campylobacter gastroenteritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Cellulitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Clostridium difficile colitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Diverticulitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Gastroenteritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	3/153 (1.96%)	3	0/51 (0.00%)	0	1/51 (1.96%)	1
Gastroenteritis viral † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Gastrointestinal viral infection † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Lower respiratory tract infection † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Lower respiratory tract infection bacterial † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Meningitis aseptic † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Metapneumovirus infection † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Mycoplasma infection † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Parainfluenzae virus infection † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Pneumonia † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	1/51 (1.96%)	1	2/51 (3.92%)	2
Pyelonephritis † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Viral infection † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	0/51 (0.00%)	0	1/51 (1.96%)	1
Wound infection † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Wound infection bacterial † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
COVID-19 pneumonia † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Injury, poisoning and procedural complications
Accidental overdose † 1	1/22 (4.55%)	3	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Muscle injury † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Subdural haematoma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	1/51 (1.96%)	1
Tibia fracture † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Investigations
Pancreatic enzymes increased † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Diabetic ketoacidosis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Hypercalcaemia † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	2	0/51 (0.00%)	0	0/51 (0.00%)	0
Hyperglycaemia † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Hyponatraemia † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	1/51 (1.96%)	1
Type 1 diabetes mellitus † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	3/153 (1.96%)	3	0/51 (0.00%)	0	0/51 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Back pain † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Rhabdomyolysis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Basal cell carcinoma † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	3	2/51 (3.92%)	2	2/51 (3.92%)	3
Basosquamous carcinoma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Breast cancer † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Cancer pain † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Invasive ductal breast carcinoma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Invasive lobular breast carcinoma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Keratoacanthoma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Malignant melanoma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	1/51 (1.96%)	2	0/51 (0.00%)	0
Metastases to central nervous system † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Metastatic renal cell carcinoma † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Squamous cell carcinoma † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	2/51 (3.92%)	2	3/51 (5.88%)	3
Squamous cell carcinoma of skin † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
T-cell lymphoma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Nervous system disorders
Auditory nerve disorder † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Brain stem stroke † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Epilepsy † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Headache † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
IIIrd nerve disorder † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Intracranial mass † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Memory impairment † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Migraine † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Optic neuritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Peripheral sensorimotor neuropathy † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Peripheral sensory neuropathy † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Presyncope † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Seizure † 1	0/22 (0.00%)	0	1/14 (7.14%)	3	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
VIth nerve paralysis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Intraventricular haemorrhage † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Psychiatric disorders
Agitation † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Confusional state † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Depression † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	1/3 (33.33%)	1	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Drug abuse † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Mania † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Personality change † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Suicide attempt † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Renal and urinary disorders
Glomerulonephritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Nephrolithiasis † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Tubulointerstitial nephritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	0/51 (0.00%)	0	0/51 (0.00%)	0
Urinary incontinence † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Haemoptysis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Pleural effusion † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Pneumonia aspiration † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Pneumonitis † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	1/3 (33.33%)	1	4/153 (2.61%)	4	1/51 (1.96%)	1	2/51 (3.92%)	2
Pulmonary embolism † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Respiratory disorder † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Precancerous skin lesion † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	0/51 (0.00%)	0	0/51 (0.00%)	0
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part 1A Pembrolizumab + IPI 1 mg/kg		Part 1A Pembrolizumab + PEG-IFN 1 µg/kg		Part 1A Pembrolizumab + PEG-IFN 2 µg/kg		Part 1B Pembrolizumab + IPI 1 mg/kg		Part 1C Pembrolizumab + IPI 50 mg		Part 1C Pembrolizumab + IPI 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/22 (100.00%)		14/14 (100.00%)		3/3 (100.00%)		152/153 (99.35%)		51/51 (100.00%)		51/51 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	2/22 (9.09%)	2	7/14 (50.00%)	14	0/3 (0.00%)	0	6/153 (3.92%)	10	2/51 (3.92%)	2	8/51 (15.69%)	13
Leukopenia † 1	0/22 (0.00%)	0	1/14 (7.14%)	3	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	2	0/51 (0.00%)	0
Lymphadenopathy † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Microcytic anaemia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Neutropenia † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	2/153 (1.31%)	2	1/51 (1.96%)	2	0/51 (0.00%)	0
Thrombocytopenia † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	2/153 (1.31%)	2	1/51 (1.96%)	2	0/51 (0.00%)	0
Cardiac disorders
Atrial fibrillation † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	3/153 (1.96%)	3	0/51 (0.00%)	0	0/51 (0.00%)	0
Sinus bradycardia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Ear and labyrinth disorders
Vertigo † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	6/153 (3.92%)	7	1/51 (1.96%)	1	3/51 (5.88%)	3
Endocrine disorders
Adrenal insufficiency † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	4/153 (2.61%)	4	3/51 (5.88%)	3	2/51 (3.92%)	2
Hyperthyroidism † 1	3/22 (13.64%)	3	2/14 (14.29%)	2	0/3 (0.00%)	0	14/153 (9.15%)	14	4/51 (7.84%)	4	3/51 (5.88%)	3
Hypophysitis † 1	3/22 (13.64%)	3	0/14 (0.00%)	0	0/3 (0.00%)	0	13/153 (8.50%)	13	0/51 (0.00%)	0	3/51 (5.88%)	3
Hypothyroidism † 1	3/22 (13.64%)	3	1/14 (7.14%)	1	0/3 (0.00%)	0	27/153 (17.65%)	28	8/51 (15.69%)	9	10/51 (19.61%)	10
Eye disorders
Abnormal sensation in eye † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Astigmatism † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Cataract † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Conjunctival haemorrhage † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Diplopia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Dry eye † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	6/153 (3.92%)	7	5/51 (9.80%)	5	1/51 (1.96%)	1
Eyelid ptosis † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Ocular hyperaemia † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	3/51 (5.88%)	3	1/51 (1.96%)	1
Photophobia † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Vision blurred † 1	2/22 (9.09%)	2	1/14 (7.14%)	1	1/3 (33.33%)	1	10/153 (6.54%)	12	4/51 (7.84%)	4	5/51 (9.80%)	5
Gastrointestinal disorders
Abdominal discomfort † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	5/153 (3.27%)	7	0/51 (0.00%)	0	1/51 (1.96%)	1
Abdominal distension † 1	3/22 (13.64%)	3	0/14 (0.00%)	0	0/3 (0.00%)	0	6/153 (3.92%)	8	2/51 (3.92%)	3	3/51 (5.88%)	3
Abdominal pain † 1	5/22 (22.73%)	6	3/14 (21.43%)	3	0/3 (0.00%)	0	22/153 (14.38%)	25	7/51 (13.73%)	9	12/51 (23.53%)	18
Abdominal pain upper † 1	2/22 (9.09%)	3	0/14 (0.00%)	0	0/3 (0.00%)	0	10/153 (6.54%)	13	7/51 (13.73%)	9	1/51 (1.96%)	1
Colitis † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	5/153 (3.27%)	5	2/51 (3.92%)	2	4/51 (7.84%)	6
Constipation † 1	3/22 (13.64%)	3	2/14 (14.29%)	3	0/3 (0.00%)	0	33/153 (21.57%)	41	9/51 (17.65%)	11	10/51 (19.61%)	10
Diarrhoea † 1	6/22 (27.27%)	12	5/14 (35.71%)	8	2/3 (66.67%)	4	60/153 (39.22%)	125	23/51 (45.10%)	41	24/51 (47.06%)	57
Dry mouth † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	34/153 (22.22%)	34	6/51 (11.76%)	6	9/51 (17.65%)	9
Dyspepsia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	5/153 (3.27%)	5	5/51 (9.80%)	5	2/51 (3.92%)	2
Dysphagia † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Flatulence † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	1/3 (33.33%)	1	1/153 (0.65%)	1	2/51 (3.92%)	2	0/51 (0.00%)	0
Frequent bowel movements † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Gastrooesophageal reflux disease † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	9/153 (5.88%)	13	2/51 (3.92%)	2	3/51 (5.88%)	4
Haemorrhoids † 1	1/22 (4.55%)	1	2/14 (14.29%)	2	0/3 (0.00%)	0	3/153 (1.96%)	3	0/51 (0.00%)	0	1/51 (1.96%)	1
Mouth haemorrhage † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Nausea † 1	5/22 (22.73%)	5	7/14 (50.00%)	9	1/3 (33.33%)	2	59/153 (38.56%)	78	14/51 (27.45%)	17	23/51 (45.10%)	29
Oral pain † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Rectal haemorrhage † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	1/51 (1.96%)	1
Retching † 1	3/22 (13.64%)	4	0/14 (0.00%)	0	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Toothache † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	5/153 (3.27%)	6	1/51 (1.96%)	1	1/51 (1.96%)	1
Vomiting † 1	4/22 (18.18%)	4	2/14 (14.29%)	2	1/3 (33.33%)	2	35/153 (22.88%)	44	7/51 (13.73%)	8	12/51 (23.53%)	14
General disorders
Asthenia † 1	2/22 (9.09%)	2	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	6/51 (11.76%)	11	4/51 (7.84%)	5
Chest pain † 1	3/22 (13.64%)	3	1/14 (7.14%)	1	0/3 (0.00%)	0	6/153 (3.92%)	6	2/51 (3.92%)	2	2/51 (3.92%)	3
Chills † 1	2/22 (9.09%)	2	5/14 (35.71%)	9	2/3 (66.67%)	3	11/153 (7.19%)	13	6/51 (11.76%)	6	0/51 (0.00%)	0
Fatigue † 1	9/22 (40.91%)	12	11/14 (78.57%)	17	3/3 (100.00%)	3	89/153 (58.17%)	117	31/51 (60.78%)	51	34/51 (66.67%)	43
Gait disturbance † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	1/3 (33.33%)	1	1/153 (0.65%)	1	1/51 (1.96%)	1	1/51 (1.96%)	1
Influenza like illness † 1	0/22 (0.00%)	0	3/14 (21.43%)	7	1/3 (33.33%)	1	23/153 (15.03%)	37	11/51 (21.57%)	15	10/51 (19.61%)	13
Injection site erythema † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Injection site pain † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Injection site rash † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Injection site reaction † 1	0/22 (0.00%)	0	2/14 (14.29%)	3	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Mucosal inflammation † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	2/51 (3.92%)	2	2/51 (3.92%)	2
Non-cardiac chest pain † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	3/51 (5.88%)	3	0/51 (0.00%)	0
Oedema peripheral † 1	2/22 (9.09%)	2	1/14 (7.14%)	1	1/3 (33.33%)	1	4/153 (2.61%)	5	6/51 (11.76%)	7	5/51 (9.80%)	6
Pain † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Peripheral swelling † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	3/153 (1.96%)	3	2/51 (3.92%)	3	1/51 (1.96%)	1
Pyrexia † 1	5/22 (22.73%)	5	5/14 (35.71%)	12	2/3 (66.67%)	3	20/153 (13.07%)	25	7/51 (13.73%)	10	3/51 (5.88%)	3
Xerosis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	3/51 (5.88%)	3	1/51 (1.96%)	1
Chest discomfort † 1	0/22 (0.00%)	0	1/14 (7.14%)	2	0/3 (0.00%)	0	4/153 (2.61%)	5	1/51 (1.96%)	1	2/51 (3.92%)	3
Hepatobiliary disorders
Autoimmune hepatitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	8/153 (5.23%)	9	1/51 (1.96%)	1	3/51 (5.88%)	3
Drug-induced liver injury † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Immune system disorders
Seasonal allergy † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	6/153 (3.92%)	7	1/51 (1.96%)	1	3/51 (5.88%)	3
Infections and infestations
Bronchitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	3/153 (1.96%)	4	1/51 (1.96%)	1	3/51 (5.88%)	5
Conjunctivitis † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	8/153 (5.23%)	8	4/51 (7.84%)	4	5/51 (9.80%)	5
Gastroenteritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	3	3/51 (5.88%)	5	0/51 (0.00%)	0
Influenza † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	12/153 (7.84%)	14	1/51 (1.96%)	1	2/51 (3.92%)	2
Lower respiratory tract infection † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	13/153 (8.50%)	16	0/51 (0.00%)	0	1/51 (1.96%)	1
Nasopharyngitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	10/153 (6.54%)	10	4/51 (7.84%)	6	3/51 (5.88%)	4
Oral candidiasis † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	8/153 (5.23%)	8	1/51 (1.96%)	1	2/51 (3.92%)	3
Oral herpes † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	9/153 (5.88%)	11	1/51 (1.96%)	1	2/51 (3.92%)	2
Pneumonia † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	4/153 (2.61%)	4	3/51 (5.88%)	3	2/51 (3.92%)	2
Rhinitis † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	6/153 (3.92%)	7	2/51 (3.92%)	2	0/51 (0.00%)	0
Sinusitis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	17/153 (11.11%)	22	5/51 (9.80%)	6	1/51 (1.96%)	1
Upper respiratory tract infection † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	36/153 (23.53%)	50	9/51 (17.65%)	10	8/51 (15.69%)	10
Urinary tract infection † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	1/3 (33.33%)	2	15/153 (9.80%)	19	1/51 (1.96%)	3	6/51 (11.76%)	7
Injury, poisoning and procedural complications
Arthropod bite † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Contusion † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	4/153 (2.61%)	4	2/51 (3.92%)	2	4/51 (7.84%)	4
Fall † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	4/153 (2.61%)	4	5/51 (9.80%)	5	0/51 (0.00%)	0
Pseudomeningocele † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Wound † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	5/22 (22.73%)	5	3/14 (21.43%)	3	2/3 (66.67%)	3	24/153 (15.69%)	28	10/51 (19.61%)	19	6/51 (11.76%)	7
Amylase increased † 1	2/22 (9.09%)	2	1/14 (7.14%)	1	1/3 (33.33%)	1	30/153 (19.61%)	35	2/51 (3.92%)	2	7/51 (13.73%)	10
Aspartate aminotransferase increased † 1	4/22 (18.18%)	4	4/14 (28.57%)	5	2/3 (66.67%)	3	20/153 (13.07%)	24	10/51 (19.61%)	12	7/51 (13.73%)	9
Blood alkaline phosphatase increased † 1	1/22 (4.55%)	1	3/14 (21.43%)	5	0/3 (0.00%)	0	10/153 (6.54%)	10	2/51 (3.92%)	2	4/51 (7.84%)	8
Blood creatine increased † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Blood creatine phosphokinase increased † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	9/153 (5.88%)	10	3/51 (5.88%)	5	0/51 (0.00%)	0
Blood creatinine increased † 1	0/22 (0.00%)	0	3/14 (21.43%)	4	0/3 (0.00%)	0	12/153 (7.84%)	13	3/51 (5.88%)	3	3/51 (5.88%)	3
Blood potassium increased † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Blood thyroid stimulating hormone decreased † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	4/153 (2.61%)	4	4/51 (7.84%)	4	1/51 (1.96%)	1
Blood thyroid stimulating hormone increased † 1	0/22 (0.00%)	0	1/14 (7.14%)	2	0/3 (0.00%)	0	1/153 (0.65%)	1	3/51 (5.88%)	3	0/51 (0.00%)	0
Breath sounds abnormal † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Gamma-glutamyltransferase increased † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	14/153 (9.15%)	14	3/51 (5.88%)	3	4/51 (7.84%)	4
Lipase increased † 1	4/22 (18.18%)	10	1/14 (7.14%)	1	1/3 (33.33%)	1	39/153 (25.49%)	55	11/51 (21.57%)	14	14/51 (27.45%)	21
Lymphocyte count decreased † 1	0/22 (0.00%)	0	3/14 (21.43%)	3	0/3 (0.00%)	0	0/153 (0.00%)	0	2/51 (3.92%)	2	1/51 (1.96%)	1
Neutrophil count decreased † 1	0/22 (0.00%)	0	5/14 (35.71%)	13	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Platelet count decreased † 1	0/22 (0.00%)	0	3/14 (21.43%)	8	0/3 (0.00%)	0	2/153 (1.31%)	3	1/51 (1.96%)	1	0/51 (0.00%)	0
Thyroxine free decreased † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	3/51 (5.88%)	3	1/51 (1.96%)	1
Thyroxine free increased † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	3/51 (5.88%)	3	0/51 (0.00%)	0
Tri-iodothyronine free decreased † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	3/51 (5.88%)	3	0/51 (0.00%)	0
Tri-iodothyronine free increased † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	3/51 (5.88%)	3	0/51 (0.00%)	0
Weight decreased † 1	2/22 (9.09%)	2	3/14 (21.43%)	3	0/3 (0.00%)	0	6/153 (3.92%)	7	1/51 (1.96%)	1	3/51 (5.88%)	3
Weight increased † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
White blood cell count decreased † 1	0/22 (0.00%)	0	5/14 (35.71%)	9	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	5/22 (22.73%)	6	6/14 (42.86%)	7	1/3 (33.33%)	1	29/153 (18.95%)	32	8/51 (15.69%)	8	14/51 (27.45%)	14
Dehydration † 1	3/22 (13.64%)	3	3/14 (21.43%)	3	0/3 (0.00%)	0	4/153 (2.61%)	4	1/51 (1.96%)	1	2/51 (3.92%)	3
Hypercalcaemia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	2/153 (1.31%)	3	1/51 (1.96%)	1	0/51 (0.00%)	0
Hyperglycaemia † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	7/153 (4.58%)	10	2/51 (3.92%)	2	1/51 (1.96%)	1
Hyperkalaemia † 1	1/22 (4.55%)	1	2/14 (14.29%)	2	1/3 (33.33%)	2	2/153 (1.31%)	2	2/51 (3.92%)	4	1/51 (1.96%)	1
Hypernatraemia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	1/51 (1.96%)	1
Hyperuricaemia † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	4/153 (2.61%)	5	1/51 (1.96%)	1	0/51 (0.00%)	0
Hypoalbuminaemia † 1	0/22 (0.00%)	0	3/14 (21.43%)	6	0/3 (0.00%)	0	1/153 (0.65%)	1	1/51 (1.96%)	2	1/51 (1.96%)	1
Hypokalaemia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	2/153 (1.31%)	2	3/51 (5.88%)	3	3/51 (5.88%)	3
Hyponatraemia † 1	3/22 (13.64%)	3	3/14 (21.43%)	5	0/3 (0.00%)	0	1/153 (0.65%)	1	1/51 (1.96%)	3	3/51 (5.88%)	3
Hypophosphataemia † 1	0/22 (0.00%)	0	3/14 (21.43%)	4	0/3 (0.00%)	0	1/153 (0.65%)	3	1/51 (1.96%)	1	2/51 (3.92%)	2
Musculoskeletal and connective tissue disorders
Arthralgia † 1	6/22 (27.27%)	12	3/14 (21.43%)	5	1/3 (33.33%)	1	41/153 (26.80%)	58	19/51 (37.25%)	27	22/51 (43.14%)	34
Arthritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	4/153 (2.61%)	4	2/51 (3.92%)	4	3/51 (5.88%)	3
Back pain † 1	2/22 (9.09%)	2	1/14 (7.14%)	1	1/3 (33.33%)	2	16/153 (10.46%)	18	9/51 (17.65%)	9	8/51 (15.69%)	11
Bone pain † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	1/51 (1.96%)	2
Flank pain † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	5/153 (3.27%)	6	1/51 (1.96%)	1	1/51 (1.96%)	2
Groin pain † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	2	3/51 (5.88%)	3	1/51 (1.96%)	1
Joint effusion † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Muscle spasms † 1	3/22 (13.64%)	3	1/14 (7.14%)	1	0/3 (0.00%)	0	9/153 (5.88%)	10	3/51 (5.88%)	3	4/51 (7.84%)	5
Muscular weakness † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	1/3 (33.33%)	1	2/153 (1.31%)	3	3/51 (5.88%)	3	2/51 (3.92%)	3
Musculoskeletal chest pain † 1	2/22 (9.09%)	2	1/14 (7.14%)	2	0/3 (0.00%)	0	11/153 (7.19%)	11	5/51 (9.80%)	5	1/51 (1.96%)	1
Musculoskeletal discomfort † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Myalgia † 1	4/22 (18.18%)	5	1/14 (7.14%)	2	1/3 (33.33%)	1	20/153 (13.07%)	22	9/51 (17.65%)	16	9/51 (17.65%)	13
Myositis † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Neck pain † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	4/153 (2.61%)	5	4/51 (7.84%)	4	3/51 (5.88%)	3
Osteoarthritis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	2/153 (1.31%)	2	0/51 (0.00%)	0	1/51 (1.96%)	1
Pain in extremity † 1	3/22 (13.64%)	3	1/14 (7.14%)	1	1/3 (33.33%)	1	14/153 (9.15%)	14	8/51 (15.69%)	10	4/51 (7.84%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroma † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Nervous system disorders
Aphasia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Dizziness † 1	4/22 (18.18%)	6	3/14 (21.43%)	6	1/3 (33.33%)	1	22/153 (14.38%)	25	5/51 (9.80%)	5	5/51 (9.80%)	6
Dysgeusia † 1	0/22 (0.00%)	0	4/14 (28.57%)	4	0/3 (0.00%)	0	4/153 (2.61%)	5	0/51 (0.00%)	0	0/51 (0.00%)	0
Headache † 1	5/22 (22.73%)	5	6/14 (42.86%)	10	1/3 (33.33%)	2	56/153 (36.60%)	68	15/51 (29.41%)	20	16/51 (31.37%)	28
Hyperaesthesia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	2/51 (3.92%)	2	0/51 (0.00%)	0
Hypoaesthesia † 1	3/22 (13.64%)	3	0/14 (0.00%)	0	0/3 (0.00%)	0	3/153 (1.96%)	3	0/51 (0.00%)	0	2/51 (3.92%)	2
Lethargy † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	14/153 (9.15%)	15	1/51 (1.96%)	1	0/51 (0.00%)	0
Memory impairment † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Neuropathy peripheral † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	7/153 (4.58%)	7	1/51 (1.96%)	2	1/51 (1.96%)	1
Paraesthesia † 1	0/22 (0.00%)	0	2/14 (14.29%)	3	0/3 (0.00%)	0	2/153 (1.31%)	3	0/51 (0.00%)	0	1/51 (1.96%)	1
Presyncope † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	1	1/51 (1.96%)	1	0/51 (0.00%)	0
Sciatica † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	4/51 (7.84%)	4	0/51 (0.00%)	0
Seizure † 1	0/22 (0.00%)	0	1/14 (7.14%)	2	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Taste disorder † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	8/153 (5.23%)	9	1/51 (1.96%)	2	1/51 (1.96%)	2
Tremor † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	2/153 (1.31%)	3	1/51 (1.96%)	1	1/51 (1.96%)	1
Psychiatric disorders
Agitation † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Anxiety † 1	1/22 (4.55%)	1	4/14 (28.57%)	4	0/3 (0.00%)	0	10/153 (6.54%)	10	2/51 (3.92%)	2	4/51 (7.84%)	4
Confusional state † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Depression † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	2/3 (66.67%)	2	6/153 (3.92%)	6	0/51 (0.00%)	0	2/51 (3.92%)	2
Hallucination † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Insomnia † 1	3/22 (13.64%)	3	4/14 (28.57%)	5	0/3 (0.00%)	0	18/153 (11.76%)	19	12/51 (23.53%)	16	10/51 (19.61%)	11
Irritability † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Sleep disorder † 1	2/22 (9.09%)	2	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Stress † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	1/3 (33.33%)	1	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Chronic kidney disease † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Haematuria † 1	0/22 (0.00%)	0	3/14 (21.43%)	3	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Micturition urgency † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Nocturia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Pollakiuria † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	6/153 (3.92%)	6	1/51 (1.96%)	1	0/51 (0.00%)	0
Proteinuria † 1	0/22 (0.00%)	0	3/14 (21.43%)	5	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Stress urinary incontinence † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	1/153 (0.65%)	2	0/51 (0.00%)	0	0/51 (0.00%)	0
Urinary incontinence † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Urinary retention † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	1/51 (1.96%)	1
Respiratory, thoracic and mediastinal disorders
Atelectasis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Chronic obstructive pulmonary disease † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	1/153 (0.65%)	1	0/51 (0.00%)	0	0/51 (0.00%)	0
Cough † 1	8/22 (36.36%)	10	9/14 (64.29%)	12	2/3 (66.67%)	2	38/153 (24.84%)	47	17/51 (33.33%)	20	11/51 (21.57%)	15
Dysphonia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	4/153 (2.61%)	4	0/51 (0.00%)	0	1/51 (1.96%)	1
Dyspnoea † 1	2/22 (9.09%)	2	1/14 (7.14%)	2	1/3 (33.33%)	1	20/153 (13.07%)	26	9/51 (17.65%)	12	5/51 (9.80%)	8
Dyspnoea exertional † 1	1/22 (4.55%)	1	2/14 (14.29%)	2	0/3 (0.00%)	0	1/153 (0.65%)	1	0/51 (0.00%)	0	1/51 (1.96%)	1
Epistaxis † 1	1/22 (4.55%)	1	2/14 (14.29%)	2	0/3 (0.00%)	0	3/153 (1.96%)	4	0/51 (0.00%)	0	1/51 (1.96%)	1
Haemoptysis † 1	0/22 (0.00%)	0	1/14 (7.14%)	2	0/3 (0.00%)	0	0/153 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
Hypoxia † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Nasal congestion † 1	4/22 (18.18%)	4	1/14 (7.14%)	1	0/3 (0.00%)	0	5/153 (3.27%)	5	5/51 (9.80%)	5	2/51 (3.92%)	3
Oropharyngeal pain † 1	2/22 (9.09%)	2	1/14 (7.14%)	1	0/3 (0.00%)	0	16/153 (10.46%)	17	1/51 (1.96%)	1	2/51 (3.92%)	2
Pneumonitis † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	16/153 (10.46%)	17	2/51 (3.92%)	2	3/51 (5.88%)	5
Productive cough † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	6/153 (3.92%)	7	2/51 (3.92%)	2	1/51 (1.96%)	1
Respiratory acidosis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Respiratory failure † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	0/153 (0.00%)	0	0/51 (0.00%)	0	0/51 (0.00%)	0
Rhinitis allergic † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	5/153 (3.27%)	5	2/51 (3.92%)	2	0/51 (0.00%)	0
Sneezing † 1	0/22 (0.00%)	0	2/14 (14.29%)	2	0/3 (0.00%)	0	1/153 (0.65%)	2	0/51 (0.00%)	0	1/51 (1.96%)	1
Upper-airway cough syndrome † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	1/3 (33.33%)	1	3/153 (1.96%)	3	1/51 (1.96%)	1	0/51 (0.00%)	0
Wheezing † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	4/153 (2.61%)	4	1/51 (1.96%)	3	0/51 (0.00%)	0
Skin and subcutaneous tissue disorders
Acne † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	3/153 (1.96%)	3	0/51 (0.00%)	0	1/51 (1.96%)	1
Actinic keratosis † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	7/153 (4.58%)	7	0/51 (0.00%)	0	4/51 (7.84%)	4
Alopecia † 1	1/22 (4.55%)	1	0/14 (0.00%)	0	1/3 (33.33%)	1	4/153 (2.61%)	5	3/51 (5.88%)	3	0/51 (0.00%)	0
Dry skin † 1	1/22 (4.55%)	1	2/14 (14.29%)	2	0/3 (0.00%)	0	11/153 (7.19%)	11	1/51 (1.96%)	1	2/51 (3.92%)	2
Eczema † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	2/153 (1.31%)	3	0/51 (0.00%)	0	3/51 (5.88%)	3
Erythema † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	8/153 (5.23%)	9	2/51 (3.92%)	3	2/51 (3.92%)	2
Hyperhidrosis † 1	1/22 (4.55%)	1	2/14 (14.29%)	2	0/3 (0.00%)	0	7/153 (4.58%)	7	2/51 (3.92%)	2	2/51 (3.92%)	2
Night sweats † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	8/153 (5.23%)	8	3/51 (5.88%)	3	1/51 (1.96%)	1
Pruritus † 1	3/22 (13.64%)	4	5/14 (35.71%)	7	2/3 (66.67%)	3	71/153 (46.41%)	98	19/51 (37.25%)	30	30/51 (58.82%)	43
Rash † 1	4/22 (18.18%)	5	5/14 (35.71%)	7	2/3 (66.67%)	3	73/153 (47.71%)	120	27/51 (52.94%)	47	24/51 (47.06%)	49
Rash macular † 1	2/22 (9.09%)	2	0/14 (0.00%)	0	0/3 (0.00%)	0	8/153 (5.23%)	9	5/51 (9.80%)	5	0/51 (0.00%)	0
Rash maculo-papular † 1	0/22 (0.00%)	0	1/14 (7.14%)	3	0/3 (0.00%)	0	22/153 (14.38%)	28	3/51 (5.88%)	3	4/51 (7.84%)	5
Rash pruritic † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	11/153 (7.19%)	11	7/51 (13.73%)	11	9/51 (17.65%)	13
Skin hypopigmentation † 1	0/22 (0.00%)	0	0/14 (0.00%)	0	0/3 (0.00%)	0	1/153 (0.65%)	1	3/51 (5.88%)	3	1/51 (1.96%)	1
Skin lesion † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	0/3 (0.00%)	0	6/153 (3.92%)	8	2/51 (3.92%)	2	1/51 (1.96%)	1
Skin mass † 1	0/22 (0.00%)	0	1/14 (7.14%)	1	0/3 (0.00%)	0	3/153 (1.96%)	4	0/51 (0.00%)	0	0/51 (0.00%)	0
Vitiligo † 1	3/22 (13.64%)	3	0/14 (0.00%)	0	0/3 (0.00%)	0	31/153 (20.26%)	31	7/51 (13.73%)	7	7/51 (13.73%)	7
Vascular disorders
Hypertension † 1	1/22 (4.55%)	1	1/14 (7.14%)	1	1/3 (33.33%)	1	8/153 (5.23%)	8	3/51 (5.88%)	3	0/51 (0.00%)	0
Hypotension † 1	2/22 (9.09%)	2	2/14 (14.29%)	2	0/3 (0.00%)	0	5/153 (3.27%)	5	1/51 (1.96%)	1	1/51 (1.96%)	1
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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 Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Long GV, Atkinson V, Cebon JS, Jameson MB, Fitzharris BM, McNeil CM, Hill AG, Ribas A, Atkins MB, Thompson JA, Hwu WJ, Hodi FS, Menzies AM, Guminski AD, Kefford R, Kong BY, Tamjid B, Srivastava A, Lomax AJ, Islam M, Shu X, Ebbinghaus S, Ibrahim N, Carlino MS. Standard-dose pembrolizumab in combination with reduced-dose ipilimumab for patients with advanced melanoma (KEYNOTE-029): an open-label, phase 1b trial. Lancet Oncol. 2017 Sep;18(9):1202-1210. doi: 10.1016/S1470-2045(17)30428-X. Epub 2017 Jul 17.

Carlino MS, Menzies AM, Atkinson V, Cebon JS, Jameson MB, Fitzharris BM, McNeil CM, Hill AG, Ribas A, Atkins MB, Thompson JA, Hwu WJ, Hodi FS, Guminski AD, Kefford R, Wu H, Ibrahim N, Homet Moreno B, Long GV. Long-term Follow-up of Standard-Dose Pembrolizumab Plus Reduced-Dose Ipilimumab in Patients with Advanced Melanoma: KEYNOTE-029 Part 1B. Clin Cancer Res. 2020 Oct 1;26(19):5086-5091. doi: 10.1158/1078-0432.CCR-20-0177. Epub 2020 Jun 30.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Atkins MB, Hodi FS, Thompson JA, McDermott DF, Hwu WJ, Lawrence DP, Dawson NA, Wong DJ, Bhatia S, James M, Jain L, Robey S, Shu X, Homet Moreno B, Perini RF, Choueiri TK, Ribas A. Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE-029 Study. Clin Cancer Res. 2018 Apr 15;24(8):1805-1815. doi: 10.1158/1078-0432.CCR-17-3436. Epub 2018 Jan 22.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02089685
• Other Study ID Numbers: 3475-029; MK-3475-029 ( Other Identifier: Merck ); KEYNOTE-29 ( Other Identifier: Merck ); 2013-004072-36 ( EudraCT Number )
• First Submitted: March 14, 2014
• First Posted: March 18, 2014
• Results First Submitted: March 22, 2022
• Results First Posted: May 18, 2022
• Last Update Posted: September 13, 2022