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

Abstract

4504 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