Studying the Side Effects of Different Dosing Strategies of Nivolumab and Pembrolizumab for the Treatment of Solid Tumors

PRIMARY OBJECTIVE:

I. To compare proportions of grade ≥ 3 immune-related adverse events (irAEs) between the two arms in each cohort.

SECONDARY OBJECTIVES:

I. To assess all grades of irAEs.

II. To assess time to resolution of irAEs.

III. To assess treatment discontinuation due to irAEs.

IV. To assess overall response rate (ORR) at 3 months (for advanced cancers / participants with measurable disease) per Response Evaluation Criteria in Solid Tumors (RECIST) and Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST).

V. To assess 6 month, 1 year (yr) and 2 yr disease free survival (DFS)/progression free survival (PFS).

VI. To assess 1 year and 2 year overall survival.

TERTIARY/EXPLORATORY OBJECTIVES:

I. To assess complete molecular response rate in each cohort.

II. To assess the correlation between the depth of molecular response to PFS/OS in each cohort.

III. To assess the correlation between the time to maximum molecular response to PFS/OS in each cohort.

IV. To assess durability of molecular response in each cohort.

V. To evaluate the correlation between time to molecular progression to PFS/OS in each cohort.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

NIVOLUMAB COHORT: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive nivolumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 2 weeks for up to 12 weeks in the absence of disease progression or unacceptable toxicity. After 12 weeks of treatment tolerance and at treating physician discretion, nivolumab dosing and cycle length may be changed and patients receive nivolumab IV on day 1 of each cycle. Cycles then repeat every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

PEMBROLIZUMAB COHORT: Patients are randomized to 1 of 2 arms.

ARM III: Patients receive pembrolizumab IV on day 1 of each cycle. Cycles repeat every 3 weeks for up to 12 weeks in the absence of disease progression or unacceptable toxicity. After 12 weeks of treatment tolerance and at treating physician discretion, pembrolizumab dosing and cycle length may be changed and patients receive pembrolizumab IV on day 1 of each cycle. Cycles then repeat every 3 or 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM IV: Patients receive pembrolizumab IV on day 1 of each cycle. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Additionally, all patients undergo computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) throughout the study. Patients may also optionally undergo archived tissue sample collection during screening and blood sample collection on study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months until withdraw, death, or end of study whichever comes first.