Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC).

Genitourinary (Nonprostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Nonprostate) Cancer
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 4504)
Hans J. Hammers, Elizabeth R. Plimack, Jeffrey R. Infante, Marc S. Ernstoff, Brian I. Rini, David F. McDermott, Albiruni R. A. Razak, 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, Asim Amin; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; 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; Levine Cancer Institute, Charlotte, NC

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Abstract Disclosures


Background: There is a need for agents that result in durable responses and improved tolerability in patients (pts) with mRCC. Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has shown activity in mRCC. Combining nivolumab + ipilimumab, a fully human monoclonal antibody to CTLA-4, showed encouraging clinical activity and acceptable safety in advanced melanoma. We report preliminary results of the combination in mRCC. Methods: Pts with mRCC (favorable/intermediate MSKCC score; Karnofsky performance status ≥80%; untreated or any number of prior therapies) were randomized to receive nivolumab 3 mg/kg + ipilimumab 1 mg/kg (arm N3 + I1) or nivolumab 1 mg/kg + ipilimumab 3 mg/kg (arm N1 + I3) IV Q3W for 4 doses then nivolumab 3 mg/kg IV Q2W until progression/toxicity. The primary objective was to assess safety/tolerability; secondary objective was to assess antitumor activity. Results: Pts were randomized to N3 + I1 (n=21) and N1 + I3 (n=23). Most pts (n=34; 77%) had prior systemic therapy (N3 + I1: 16; N1 + I3: 18). Treatment-related adverse events (AEs) were seen in 39/44 pts (89%); 7 pts (16%; N3 + I1: 2; N1 + I3: 5) discontinued due to any-grade related AEs. Grade 3–4 related AEs occurred in 19 pts (43%; N3 + I1: 5; N1 + I3: 14), most commonly ↑ lipase (16%, n=7), ↑ ALT (11%, n=5), diarrhea (9%, n=4), colitis (5%, n=2), ↑ amylase (5%, n=2). No grade 3–4 pneumonitis was seen. Objective response rate (ORR) was 29% (N3 + I1) and 39% (N1 + I3) (Table). Duration of response (DOR) was 4.1+ to 22.1+ wks (all 6 responses ongoing) in N3 + I1, and 6.1+ to 18.3+ wks (8/9 responses ongoing) in N1 + I3. Responses occurred by first tumor assessment (wk 6) in 67% of responding pts in both N3 + I1 and N1 + I3. Stable disease (SD) was seen in 7 (33%) pts (N3 + I1) and 9 (39%) pts (N1 + I3). Conclusions: Nivolumab + ipilimumab showed acceptable safety and encouraging antitumor activity in mRCC, with most responses ongoing. Follow-up, expansion cohorts at these doses and an additional dose cohort (nivolumab 3 mg/kg + ipilimumab 3 mg/kg) are being assessed. Clinical trial information: NCT01472081.

Arm N3 + I1 n=21 Arm N1 + I3 n=23
ORR, n (%) 6 (29) 9 (39)
SD, n (%) [duration, wks] 7 (33) [6+ to 25+] 9 (39) [6+to 26.1]
DOR, range (wks) 4.1+ – 22.1+ 6.1+ – 18.3+
PFS, range (wks) 4.7+ – 28.1+ 4.3 – 26.1