A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients

OS was measured in months from the time of randomization to the event date (death) due to any cause. A participant who has not died will be censored at the last known alive date. Based on Kaplan-Meier Estimates. Hazard ratio from Cox proportional hazard model stratified by presence of measurable lesions at baseline per IVRS. P-value from log-rank test stratified by presence of measurable lesions at baseline per IVRS.

Time frame: Time between the date of randomization and the date of death due to any cause (up to up to 17Jun2019, approximately 5 years)

Population: All Randomized Participants in Cohort 2

The percentage of participants who experienced an adverse event by worst grade in each treatment arm. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

Time frame: From first dose to 30 days post last dose (up to approximately 34 months).

Population: All Treated Participants in Cohorts 1, 1b, 1c and 1d

The percentage of participants who experienced a drug-related adverse event leading to drug discontinuation by worst grade (grade 5 being the worst) prior to complete four-dose treatment. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

Time frame: Includes events reported between first dose and 30 days after last dose of study therapy (up to 3 doses, up to approximately 2 months)

Population: All Treated Participants in Cohorts 1, 1b, 1c and 1d Who Permanently Discontinued Study Medication Prior to Completing Four Doses

The percentage of participants who experienced a serious adverse event by worst grade in each treatment arm. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

Time frame: From first dose to 30 days post last dose (up to approximately 34 months).

Population: All Treated Participants in Cohorts 1, 1b, 1c and 1d

The percentage of participants who experienced a laboratory abnormality of the liver in each treatment arm. MedDRA Version: 24.1 Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Denominator corresponds to participants with at least on one treatment measurement of the corresponding laboratory parameter. Includes laboratory results reported after the first dose and within 30 days of last dose of study therapy.

Time frame: From first dose to 30 days post last dose (up to approximately 34 months).

Population: All Treated Subjects in Cohorts 1, 1b, 1c and 1d with at least one on-treatment measurement of the corresponding laboratory parameter

The percentage of participants who experienced a laboratory abnormality of the thyroid in each treatment arm. MedDRA Version: 24.1 Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN) (A) Within a 2-week window after the abnormal TSH test date. (B) Includes participants with TSH abnormality and with no FT3/FT4 test values in the 2-week window or with non-abnormal value(s) from only one of the two tests and no value from the other test.

Time frame: From first dose to 30 days post last dose (up to approximately 34 months).

Population: All Treated Subjects in Cohorts 1, 1b, 1c and 1d with at Least One On-Treatment TSH measurement

ORR was measured by the percentage of participants whose best overall response (BOR) is confirmed Complete Response (CR) or Partial Response (PR) divided by response evaluable participants. The best overall response (BOR) is determined once all the data for the participant is known. BOR is defined as the best response designation, as determined by investigators, recorded between the date of randomization and the date of objectively documented progression per RANO criteria, the date of subsequent therapy, or date of surgical resection, whichever occurs first. Confidence interval based on the Clopper and Pearson method. For the comparison of the odds ratio of Nivolumab over Bevacizumab, the Cochran-Mantel-Haenszel (CMH) method of weighting was utilized.

Time frame: Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 10 years and 5 months)

Population: All Response Evaluable Participants in Cohort 2

OS(12) is measured as the percentage of participants alive at 12 months per Kaplan-Meier curve of OS. Z test with variance estimation based on Greenwood formula using log(-log) transformation.

Time frame: From randomization to 12 months following randomization

Population: All Randomized Participants in Cohort 2

OS was measured in months from the time of randomization (Part B) or time of treatment (Part A) to the event date (death) due to any cause. A participant who has not died will be censored at the last known alive date. Based on Kaplan-Meier Estimates.

Time frame: Time between the date of randomization and the date of death due to any cause (up to approximately 10 years and 5 months)

Population: All Randomized (Part B) or Treated (Part A) Participants in Cohorts 1c and 1d

PFS was measured in months from the time of randomization to the date of the first documented tumor progression or death due to any cause. Based on Kaplan-Meier Estimates. Hazard ratio from Cox proportional hazard model stratified by presence of measurable lesions at baseline per IVRS.

Time frame: Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 10 years and 5 months)

Population: All Randomized Participants in Cohort 2

OS was measured in months from the time of randomization to the event date (death) due to any cause. A participant who has not died will be censored at the last known alive date. Based on Kaplan-Meier Estimates. Hazard ratio from Cox proportional hazard model stratified by presence of measurable lesions at baseline per IVRS. P-value from log-rank test stratified by presence of measurable lesions at baseline per IVRS.

Time frame: Time between the date of randomization and the date of death due to any cause (up to approximately 10 years and 5 months)

Population: All Randomized Participants in Cohort 2