Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC).

Genitourinary (Nonprostate) Cancer
Session Type and Session Title: 
Clinical Science Symposium, Unleashing the Immune System in Genitourinary Cancers
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 5010)
Asim Amin, Elizabeth R. Plimack, Jeffrey R. Infante, Marc S. Ernstoff, Brian I. Rini, David F. McDermott, Jennifer J. Knox, Sumanta Kumar Pal, Martin Henner Voss, Padmanee Sharma, Christian K. Kollmannsberger, Daniel Yick Chin Heng, Jennifer L. Spratlin, Yun Shen, John F. Kurland, Paul Gagnier, Hans J. Hammers; Levine Cancer Institute, Charlotte, NC; Fox Chase Cancer Center, Philadelphia, PA; Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN; Dartmouth Hitchcock Medical Center, Geisel School of Medicine, Norris Cotton Cancer Center, Lebanon, NH; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA; Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; City of Hope Comprehensive Cancer Center, Duarte, CA; Memorial Sloan Kettering Cancer Center, New York, NY; MD Anderson Cancer Center, University of Texas, Houston, TX; British Columbia Cancer Agency, Vancouver, BC, Canada; Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada; Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; Bristol-Myers Squibb, Princeton, NJ; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD

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Abstract Disclosures


Background: Antiangiogenic agents sunitinib (S) and pazopanib (P) are SOC for mRCC, but new therapies are needed as pts advance through therapy with limited survival benefit. We report preliminary results of a phase I trial of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, in combination with S or P in pts with mRCC. Methods: mRCC patients (≥1 prior systemic therapy) received nivolumab in combination with S (50 mg, 4 wks on, 2 wks off; arm S) or P (800 mg daily; arm P), until progression/unacceptable toxicity. Starting dose of nivolumab was 2 mg/kg IV Q3W (N2), with planned escalation to 5mg/kg IV Q3W (N5). Based on tolerability, arm S N5 cohort was expanded to treatment-naïve pts. Primary objectives were safety/tolerability and determination of maximum tolerated dose (MTD) for the combinations; secondary objective was antitumor activity (objective response rate [ORR] and duration of response [DOR]). Results: 7 pts were assigned to each of arms S N2 and N5. No dose-limiting toxicities (DLTs) were observed and MTD was not reached thus N5 was expanded with 19 additional pts (total n=33). Arm P enrolled 20 pts at N2; 4 DLTs (elevated ALT/AST [n=3], fatigue [n=1]) were observed, leading to closure of this arm. Grade 3–4 related AEs were observed in 24/33 pts (73%) in arm S and 12/20 pts (60%) in arm P. Most common related grade 3–4 AEs included elevated ALT (18%), hypertension and hyponatremia (15% each) in arm S and elevated ALT/ AST (20% each) and fatigue (15%) in arm P. Hepatotoxicities were manageable using treatment algorithms. Grade 3 pneumonitis occurred in 1 pt (arm S, N5). Grade 3–4 related AEs led to therapy discontinuation in 8/33 pts (24%; 1 N2, 7 N5) in arm S and 4/20 pts (20%) in arm P. ORR was 52% (17/33) in arm S and 45% (9/20) in arm P. Responses occurred by first assessment (6 wks) in 41% (arm S) and 56% (arm P) of responding pts and were durable (range: arm S: 12.1+ to 54 wks; arm P: 12.1 to 69.1+ wks). Stable disease rate was 33% (n=11) in arm S and 35% (n=7) in arm P. PFS rate at 24 wks was 78% for arm S and 55% for arm P. Conclusions: Nivolumab plus S or P showed encouraging antitumor activity and a manageable safety profile in pts with mRCC. Additional follow up will be presented. Clinical trial information: NCT01472081.