Nivolumab with or without Ipilimumab as Front Line Therapy in Treating Patients with Advanced Kidney Cancer

Summary

Objectives

PRIMARY OBJECTIVE:
I. Determine the progression-free survival (PFS) rate at 1 year of nivolumab in patients with treatment naive clear cell renal cell cancer (ccRCC) based on tumor PD-L1 expression.

SECONDARY OBJECTIVES:
I. Determine the PFS rate at 1 year- by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune related (ir)RECIST of nivolumab in patients with treatment naive ccRCC based on the PD1- blockade durable response predictive (PRP) biomarker model developed in the Dana–Farber/Harvard Cancer Center (DFHCC) Kidney Cancer Specialized Program in Research Excellence (SPORE).
II. Determine the objective response rate (complete response [CR]/partial response [PR]=objective response rate [ORR]), the ORR based on PDL1 expression and the PRP model, and duration of response for nivolumab in patients with treatment naive ccRCC.
III. Determine the response rate of combined nivolumab and ipilimumab therapy at the time of nivolumab failure (or lack of response at 1 year).
IV. Determine the clinical activity (CR, PR and stable disease [SD]) and PFS at 1 year of nivolumab in patients with treatment naive non-clear cell (ncc)RCC.
V. Assess the toxicity of nivolumab monotherapy in patients with treatment naive cc or nccRCC.

CORRELATIVE/EXPLORATORY OBJECTIVES:
I. Explore novel potential predictive biomarkers for patients with treatment naive ccRCC and nccRCC.
II. Explore the mechanisms of innate and acquired resistance to nivolumab therapy in treatment naive patients with ccRCC.
III. Identify biomarkers associated with response to nivolumab + ipilimumab in patients whose disease has not responded or progressed on nivolumab monotherapy.

OUTLINE: Patients are assigned to 1 of 2 parts.

PART A: Patients receive nivolumab intravenously (IV) over 60 minutes on days 1, 15, and 29. Treatment repeats every 42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on days 1 and 22. Cycles repeat every 42 days for up to 96 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent progressive disease may be enrolled to Part B.

PART B: Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on days 1 and 22. Treatment repeats every 42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on days 1 and 22. Cycles repeat every 42 days for up to 48 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 3 years and then every 6 months for 2 years.