Trial Outcomes & Findings for A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (NCT NCT00730639)

Last Updated: 2021-12-03

Results Overview

AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

395 participants

Primary outcome timeframe

Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years

Results posted on

2021-12-03

Participant Flow

395 participants were enrolled and 306 were treated. 89 were not treated because they failed to meet study eligibility criteria or died prior to the initiation of treatment. All participants had received at least 1 prior cancer therapy. Study is on-going.

Participant milestones

Participant milestones
Measure	0.1 mg/kg Nivolumab 0.1 milligrams (mg) of nivolumab per kilogram (kg) of body weight (mg/kg)was administered intravenously (IV) every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, partial response (PR), or stable disease (SD), who subsequently experienced confirmed PD.	0.3 mg/kg Nivolumab 0.3 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.	1.0 mg/kg Nivolumab 1.0 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.	3.0 mg/kg Nivolumab 3.0 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.	10 mg/kg Nivolumab 10 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.
Overall Study STARTED	17	18	86	54	131
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	17	18	86	54	131

Reasons for withdrawal

Reasons for withdrawal
Measure	0.1 mg/kg Nivolumab 0.1 milligrams (mg) of nivolumab per kilogram (kg) of body weight (mg/kg)was administered intravenously (IV) every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, partial response (PR), or stable disease (SD), who subsequently experienced confirmed PD.	0.3 mg/kg Nivolumab 0.3 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.	1.0 mg/kg Nivolumab 1.0 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.	3.0 mg/kg Nivolumab 3.0 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.	10 mg/kg Nivolumab 10 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.
Overall Study Adverse Event	3	0	9	8	23
Overall Study Complete Response	0	0	2	2	1
Overall Study Completed Maximum Cycles	0	0	11	3	6
Overall Study Death	0	0	0	0	2
Overall Study Disease Progression	12	13	48	32	88
Overall Study non-specified	0	0	4	2	3
Overall Study Protocol Violation	0	0	1	0	0
Overall Study Withdrawal by Subject	0	0	6	3	4
Overall Study Treatment on-going	2	5	5	4	4

Baseline Characteristics

A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	0.1 mg/kg Nivolumab n=17 Participants Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	0.3 mg/kg Nivolumab n=18 Participants 0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	1.0 mg/kg Nivolumab n=86 Participants 1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	3.0 mg/kg Nivolumab n=54 Participants 3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	10 mg/kg Nivolumab n=131 Participants 10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	Total n=306 Participants Total of all reporting groups
Age, Continuous	57.5 years n=93 Participants	60.8 years n=4 Participants	61.8 years n=27 Participants	62.7 years n=483 Participants	63.1 years n=36 Participants	62.2 years n=10 Participants
Age, Customized Less than (<) 65 years	13 participants n=93 Participants	9 participants n=4 Participants	49 participants n=27 Participants	30 participants n=483 Participants	67 participants n=36 Participants	168 participants n=10 Participants
Age, Customized Greater than or equal to (>)= 65 years	4 participants n=93 Participants	9 participants n=4 Participants	37 participants n=27 Participants	24 participants n=483 Participants	64 participants n=36 Participants	138 participants n=10 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	9 Participants n=4 Participants	26 Participants n=27 Participants	21 Participants n=483 Participants	43 Participants n=36 Participants	103 Participants n=10 Participants
Sex: Female, Male Male	13 Participants n=93 Participants	9 Participants n=4 Participants	60 Participants n=27 Participants	33 Participants n=483 Participants	88 Participants n=36 Participants	203 Participants n=10 Participants
Tumor Type Squamous Non-Small Cell Lung Cancer (SQ NSCLC)	0 participants n=93 Participants	0 participants n=4 Participants	15 participants n=27 Participants	18 participants n=483 Participants	21 participants n=36 Participants	54 participants n=10 Participants
Tumor Type Non-Squamous NSCLC (NSQ NSCLC)	0 participants n=93 Participants	0 participants n=4 Participants	18 participants n=27 Participants	19 participants n=483 Participants	37 participants n=36 Participants	74 participants n=10 Participants
Tumor Type Melanoma	17 participants n=93 Participants	18 participants n=4 Participants	35 participants n=27 Participants	17 participants n=483 Participants	20 participants n=36 Participants	107 participants n=10 Participants
Tumor Type Renal Cell Carcinoma (RCC)	0 participants n=93 Participants	0 participants n=4 Participants	18 participants n=27 Participants	0 participants n=483 Participants	16 participants n=36 Participants	34 participants n=10 Participants
Tumor Type Castrate-Resistant Prostate Cancer (CRC)	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	19 participants n=36 Participants	19 participants n=10 Participants
Tumor Type MCRPC	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	17 participants n=36 Participants	17 participants n=10 Participants
Tumor Type NSCLC of Unspecified Histology	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants	1 participants n=10 Participants

PRIMARY outcome

Timeframe: Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years

Population: All participants who received at least 1 dose or any partial dose of nivolumab were analyzed.

Outcome measures

Outcome measures
Measure	0.1 mg/kg Nivolumab n=17 Participants Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	0.3 mg/kg Nivolumab n=18 Participants 0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	1.0 mg/kg Nivolumab n=86 Participants 1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	3.0 mg/kg Nivolumab n=54 Participants 3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	10 mg/kg Nivolumab n=131 Participants 10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	All Dose Groups All participants receiving Intravenous (IV) solution of 0.1-10 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs Discontinuation of Study Drug due to AEs	3 participants	0 participants	12 participants	12 participants	30 participants	—
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs SAE	9 participants	8 participants	37 participants	26 participants	79 participants	—
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs Treatment-Related AE	13 participants	14 participants	70 participants	40 participants	93 participants	—
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs All Deaths (within 100 days of last dose)	4 participants	4 participants	18 participants	9 participants	40 participants	—
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs Treatment-Related Deaths	0 participants	0 participants	1 participants	0 participants	1 participants	—

PRIMARY outcome

Timeframe: Day 1 up to June 2013, approximately 4 years

Population: All participants who received at least 1 dose or any partial dose of nivolumab who underwent the laboratory test.

Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine and Total Bilirubin. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Abnormal values for ALP, ALT and AST were based on grades; Gr 1: \> 1.0 - 2.5 \* upper limits of normal (ULN); Gr 2: \> 2.5 - 5.0 \* ULN; Gr 3: \> 5.0 - 20.0 \* ULN; Gr 4: \> 20.0 \* ULN. Abnormal values for Creatinine were based on Gr 1: \> 1.0 - 1.5\*ULN; Gr 2: \> 1.5 - 3.0\*ULN; Gr 3: \> 3.0 - 6.0\*ULN; Gr 4: \> 6.0\*ULN. Abnormal values for Total Bilirubin were based on Gr 1: \> 1.0 - 1.5 \* upper limits of normal (ULN); Gr 2: \> 1.5 - 3.0 \* ULN; Gr 3: \> 3.0 - 10.0 \* ULN; Gr 4: \> 10.0 \* ULN.

Outcome measures

Outcome measures
Measure	0.1 mg/kg Nivolumab n=17 Participants Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	0.3 mg/kg Nivolumab n=18 Participants 0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	1.0 mg/kg Nivolumab n=86 Participants 1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	3.0 mg/kg Nivolumab n=54 Participants 3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	10 mg/kg Nivolumab n=131 Participants 10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	All Dose Groups All participants receiving Intravenous (IV) solution of 0.1-10 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
Number of Participants With Abnormal Serum Chemistry Laboratory Values ALT (Grades 1-2)	6 participants	3 participants	25 participants	13 participants	18 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values Total Bilirubin (Grades 1-2)	2 participants	1 participants	3 participants	4 participants	3 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values Total Bilirubin (Grades 3-4)	0 participants	2 participants	0 participants	0 participants	2 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values ALP (Grades 1-2)	8 participants	7 participants	21 participants	11 participants	38 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values ALP (Grades 3-4)	0 participants	0 participants	3 participants	2 participants	3 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values ALT (Grades 3-4)	0 participants	0 participants	1 participants	2 participants	2 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values AST (Grades 1-2)	6 participants	4 participants	26 participants	13 participants	41 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values AST (Grades 3-4)	0 participants	2 participants	2 participants	3 participants	2 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values Creatinine (Grades 1-2)	5 participants	9 participants	21 participants	9 participants	34 participants	—
Number of Participants With Abnormal Serum Chemistry Laboratory Values Creatinine (Grades 3-4)	0 participants	0 participants	0 participants	0 participants	1 participants	—

PRIMARY outcome

Timeframe: Day 1 up to June 2013, approximately 4 years

Population: All participants who received at least 1 dose or any partial dose of nivolumab who underwent the laboratory test.

Hemoglobin, Lymphocytes, Neutrophils, Platelets and Leukocytes. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Abnormal values for Hemoglobin were based on Gr 1: 10.0 - less than (\<) lower limit of normal (LLN); Gr 2: 8.0 - \< 10.0; Gr 3: 6.5 - \< 8.0; Gr 4: \< 6.5. Abnormal values for Lymphocytes were based on Gr 1: 0.8 - \< 1.5; Gr 2: 0.5 - \< 0.8; Gr 3): 0.2 - \< 0.5; Gr 4: \< 0.2. Abnormal values for Neutrophils were based on Gr 1: 1.5 - \< 2.0; Gr 2: 1.0 - \< 1.5; Gr 3: 0.5 - \< 1.0; Gr 4: \< 0.5. Abnormal values for Platelets were based on Gr 1: 75.0 - \< lower limits of normal (LLN); Gr 2: 50.0 - \< 75.0; Gr 3: 25.0 - \< 50.0; Gr 4: \< 25.0. Abnormal values for Leukocytes were based on Gr 1: 3.0 - \< LLN; Gr 2: 2.0 - \< 3.0; Gr 3: 1.0 - \< 2.0; Gr4: \< 1.0.

Outcome measures

Outcome measures
Measure	0.1 mg/kg Nivolumab n=17 Participants Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	0.3 mg/kg Nivolumab n=18 Participants 0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	1.0 mg/kg Nivolumab n=86 Participants 1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	3.0 mg/kg Nivolumab n=54 Participants 3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	10 mg/kg Nivolumab n=131 Participants 10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	All Dose Groups All participants receiving Intravenous (IV) solution of 0.1-10 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
Number of Participants With Abnormal Hematology Laboratory Values Lymphocytes (Grades 3-4)	3 participants	3 participants	8 participants	8 participants	19 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Hemoglobin (Grades 1-2)	12 participants	12 participants	58 participants	46 participants	101 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Hemoglobin (Grades 3-4)	0 participants	0 participants	6 participants	0 participants	6 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Lymphocytes (Grades 1-2)	9 participants	15 participants	64 participants	43 participants	101 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Neutrophils (Grades 1-2)	4 participants	4 participants	13 participants	6 participants	12 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Neutrophils (Grades 3-4)	0 participants	0 participants	1 participants	1 participants	3 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Platelets (Grades 1-2)	2 participants	1 participants	9 participants	10 participants	19 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Platelets (Grades 3-4)	0 participants	0 participants	0 participants	0 participants	0 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Leukocytes (Grades 1-2)	4 participants	4 participants	11 participants	10 participants	13 participants	—
Number of Participants With Abnormal Hematology Laboratory Values Leukocytes (Grades 3-4)	0 participants	0 participants	1 participants	0 participants	3 participants	—

SECONDARY outcome

Timeframe: Day 1 up to June 2013, approximately 4 years

Population: All participants who received at least 1 dose or any partial dose of nivolumab and were ADA-evaluable were analyzed.

Classification of participants host immune response was based on the following definitions: Anti-Drug Antibody (ADA) Positive Subjects have with at least one ADA positive sample at any time after initiation of treatment. ADA positive subjects were further classified into categories with Persistent Positive defined as an ADA positive sample at 2 or more sequential timepoints at least 8 weeks apart.

Outcome measures

Outcome measures
Measure	0.1 mg/kg Nivolumab n=14 Participants Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	0.3 mg/kg Nivolumab n=14 Participants 0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	1.0 mg/kg Nivolumab n=66 Participants 1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	3.0 mg/kg Nivolumab n=46 Participants 3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	10 mg/kg Nivolumab n=103 Participants 10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	All Dose Groups All participants receiving Intravenous (IV) solution of 0.1-10 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
Immunogenicity Assessment Persistant Positive	1 participants	0 participants	1 participants	0 participants	0 participants	—
Immunogenicity Assessment ADA Positive	6 participants	2 participants	7 participants	2 participants	4 participants	—

SECONDARY outcome

Timeframe: Day 1 up to June 2013, approximately 4 years

Population: All participants who received at least 1 dose or any partial dose of nivolumab with an evaluable tumor response were analyzed.

Tumor response was evaluated by the sponsor based on tumor assessments by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Objective response rate (ORR) was defined as the proportion of participants who's confirmed best overall response (BOR) is either complete (CR) or partial (PR), where the denominator is the number of treated participants in the population of interest. Response was based on tumor measurements. Responders= complete response (CR) or partial response (PR). CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter. 95% Confidence intervals (CIs) were computed using the Clopper Pearson method.

Outcome measures

Outcome measures
Measure	0.1 mg/kg Nivolumab n=17 Participants Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	0.3 mg/kg Nivolumab n=18 Participants 0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	1.0 mg/kg Nivolumab n=35 Participants 1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	3.0 mg/kg Nivolumab n=37 Participants 3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	10 mg/kg Nivolumab n=59 Participants 10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.	All Dose Groups n=129 Participants All participants receiving Intravenous (IV) solution of 0.1-10 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks.
Objective Response Rate SQ NSCLC (n=0,0,15,18,21,54)	0 percentage of participants There are no participants so confidence interval was not calculated.	0 percentage of participants There are no participants so confidence interval was not calculated.	0 percentage of participants There are no participants so confidence interval was not calculated.	22.2 percentage of participants Interval 6.4 to 47.6	23.8 percentage of participants Interval 8.2 to 47.2	16.7 percentage of participants Interval 7.9 to 29.3
Objective Response Rate NSQ NSCLC (n=0,0,18,19,37,74)	0 percentage of participants There are no participants so confidence interval was not calculated.	0 percentage of participants There are no participants so confidence interval was not calculated.	5.6 percentage of participants Interval 0.1 to 27.3	26.3 percentage of participants Interval 9.1 to 51.2	18.9 percentage of participants Interval 8.0 to 35.2	17.6 percentage of participants Interval 9.7 to 28.2
Objective Response Rate TOTAL NSCLC (n=0,0,33,37,59,129)	0 percentage of participants There are no participants so confidence interval was not calculated.	0 percentage of participants There are no participants so confidence interval was not calculated.	3.0 percentage of participants Interval 0.1 to 15.8	24.3 percentage of participants Interval 11.8 to 41.2	20.3 percentage of participants Interval 11.0 to 32.8	17.1 percentage of participants Interval 11.0 to 24.7
Objective Response Rate Renal Cell Carcinoma (RCC) (n=0,0,18,0,16,34)	0 percentage of participants There are no participants so confidence interval was not calculated.	0 percentage of participants There are no participants so confidence interval was not calculated.	27.8 percentage of participants Interval 9.7 to 53.5	0 percentage of participants There are no participants so confidence interval was not calculated.	31.3 percentage of participants Interval 11.0 to 58.7	29.4 percentage of participants Interval 15.1 to 47.5
Objective Response Rate Melanoma (n=17,18,35,17,20,107)	35.3 percentage of participants Interval 14.2 to 61.7	27.8 percentage of participants Interval 9.7 to 53.5	31.4 percentage of participants Interval 16.9 to 49.3	41.2 percentage of participants Interval 18.4 to 67.1	20.0 percentage of participants Interval 5.7 to 43.7	30.8 percentage of participants Interval 22.3 to 40.5

SECONDARY outcome

Timeframe: Day 1 up to June 2013, approximately 4 years

Population: All participants who received at least 1 dose or any partial dose of nivolumab with a measurable tumor response were analyzed.

Duration of tumor response (DOR) was calculated from the first date of response of complete response (CR) or partial response (PR) to the date of the first progressive disease (PD) or the date of death. Duration of response was censored at the last tumor assessment date if a responder did not have PD or death. Nonresponders were not included in the analysis. Median DOR was estimated by Kaplan-Meier analysis.