Nivolumab and Degarelix with or without BMS-986253 in Treating Patients with Hormone-Sensitive Prostate Cancer

Summary

Objectives

PRIMARY OBJECTIVES:
I. Determine the rate of prostate-specific antigen (PSA) recurrence defined as a PSA > 0.2 ng/ml for radical prostatectomy patients or PSA > 2.0 ng/ml for patients who received other primary therapies (e.g. radiation, cryotherapy, brachytherapy) at a time point of 10 months after start of therapy.
II. Determine the safety and tolerability of either nivolumab or nivolumab plus anti-IL-8 monoclonal antibody humax-IL8 (BMS-986253) in combination with degarelix in men with hormone-sensitive prostate cancer.

SECONDARY OBJECTIVES:
I. To assess the relapse-free survival (RFS) after recovery of testosterone with relapse defined as a PSA > 0.2 ng/ml for radical prostatectomy patients or PSA > 2.0 ng/ml for patients who received other primary therapies and recovery of testosterone defined as a testosterone (> 150 ng/dl).
II. Determine the RFS with relapse defined as a PSA > 0.2 ng/ml for radical prostatectomy patients or PSA > 2.0 ng/ml for patients who received other primary therapies.
III. Determine the time to PSA > 5.0 ng/ml after start of therapy.
IV. Determine the time to recovery of testosterone in all arms of the study and measured as the time from start of therapy to the time of testosterone recovery, defined as a testosterone level > 150 ng/dl.
V. Determine the time to next anti-cancer treatment in all arms of the study and measured as the time from start of therapy to the time of next treatment.
VI. Determine the rate of metastatic progression 10 months after start of therapy.
VII. Determine the percent (%) change in PSA to immunotherapy by comparing the PSA prior to and following 8 weeks of immunotherapy and before initiation of androgen deprivation therapy (ADT).
VIII. To compare the rate of PSA recurrence at 10 months following start of therapy, RFS, RFS after recovery of testosterone, time to recovery of testosterone, time to next anti-cancer treatment and rate of metastatic progression 10 months after start of therapy between patients treated with nivolumab plus degarelix versus patients treated with nivolumab plus BMS-986253 plus degarelix.

EXPLORATORY OBJECTIVES:
I. To assess the anti-tumor immune response.
Ia. Quantification of CD8 T cell, CD4 T cell, regulatory T cells (Treg), CD8/Treg, CD4/Treg, polymorphonucler-myeloid-derived suppressor cells (PMN-MDSC) and other immune cell populations in a subset of patients (at least 10 per arm) with tumor specimens before and after treatment by immunohistochemistry (IHC).
Ib. Quantification a range of immunologic markers in a subset of patients (at least 10 per arm) with tumor specimens before and after treatment.
Ic. Quantification of tumor cell apoptosis by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay (TUNEL) and caspase-3 staining.
Id. Quantification of circulating IL-8 and other cytokines before and after treatment and correlation with response to therapy.
Ie. Quantification of circulating PMN-MDSCs and other immune cell populations before and after treatment and correlation with response to therapy.
If. Assess whether treatment can induce an increased immunoglobulin G (IgG) response to tumor antigens (epitope spreading) by comparing pre- and post-treatment sera.
Ig. Assess the deoxyribonucleic acid (DNA) or ribonucleic acid (RNA)-related molecular characteristics of tumor specimens and correlate with response to treatment (if adequate tissue available).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes and degarelix subcutaneously (SC) on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive anti-IL-8 monoclonal antibody humax-IL8 IV over 120 minutes on days 1 and 15, and nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive anti-IL-8 monoclonal antibody humax-IL8 IV over 120 minutes on days 1 and 15, nivolumab IV over 30 minutes on day 1, and degarelix SC on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 100 days, every 2 months for 1 year and then every 3 months for 1 year.