Portal de Periódicos da CAPES

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

2014; Lippincott Williams & Wilkins; Volume: 32; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2014.32.15_suppl.4504

1527-7755

Hans J. Hammers, Elizabeth R. Plimack, Jeffrey R. Infante, Marc S. Ernstoff, Brian I. Rini, David F. McDermott, Albiruni R. Abdul Razak, Sumanta K. Pal, Martin H. Voss, Padmanee Sharma, Christian Kollmannsberger, Daniel Yick Chin Heng, Jennifer L. Spratlin, Yun Shen, John F. Kurland, Paul Gagnier, Asim Amin,

Pancreatic and Hepatic Oncology Research

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