A Phase II Study of Nivolumab Combined with Ipilimumab for Patients with Advanced Rare Genitourinary Tumors
Germ Cell Tumor
18 Years and older, Male and Female
This phase II trial studies how well nivolumab and ipilimumab work in treating patients with rare genitourinary tumors that have spread to other anatomic sites or is no longer responding to treatment. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread.
I. To assess the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by tumor cohort.
I. To assess ORR across all rare genitourinary (GU) tumor types.
II. To assess duration of response (DOR) by RECIST version 1.1.
III. To assess the ORR by Immune Related Response Criteria (irRC).
IV. To assess progression-free survival (PFS) for the total cohort and by tumor type (adrenocortical carcinoma [ACC], non-urothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor).
V. To assess overall survival (OS) for the total cohort and by tumor type (ACC, nonurothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor).
VI. To assess safety and toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 4.
I. To correlate ORR by RECIST version 1.1 with programmed death ligand-1 (PDL1) tumor expression status in baseline pre-treatment biopsy.
II. To correlate ORR by RECIST version 1.1 with total exonic mutation burden as determined by whole-exome sequencing of baseline pre-treatment biopsy.
III. To correlate ORR by RECIST version 1.1 with neoantigen load as determined by whole-exome sequencing of baseline pre-treatment biopsy.
IV. To correlate ORR by RECIST version 1.1 with blood-based predictive biomarkers of response and resistance to therapy via collection of baseline, on-treatment, and progression blood specimens.
V. To assess molecular mechanisms of acquired resistance in progression biopsies in responders.
VI. To assess molecular mechanisms of response and resistance to treatment via circulating free deoxyribonucleic acid (DNA) (cfDNA) assessment and to correlate cfDNA molecular profile with metastasis biopsy molecular profile.
VII. To assess molecular mechanisms of response and resistance to treatment via circulation tumor cell (CTC) assessment and correlate CTC molecular profile with metastasis biopsy molecular profile.
Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on days 1 and 22. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 3 weeks later, patients then receive nivolumab IV over 30 minutes on days 1, 15, and 29. Courses repeat every 6 weeks in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up at 30 and 100 days and then every 24 weeks for up to 2 years.