Expanded cohort results from CheckMate 016: A phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC).

Abstract

4516 Background: Nivolumab (N), a fully human IgG4 immune checkpoint inhibitor antibody, has shown durable response and encouraging overall survival (OS) in mRCC. Previously in CheckMate 016, N + ipilimumab (I) demonstrated manageable safety and promising antitumor activity in mRCC. Here, we report results from expansion cohorts in this study (NCT01472081). Methods: Patients (pts) with mRCC were randomized to N 3 mg/kg + I 1 mg/kg (N3 + I1), N 1 mg/kg + I 3 mg/kg (N1 + I3) or N 3 mg/kg + I 3 mg/kg (N3 + I3) IV Q3W for 4 doses, then N 3 mg/kg IV Q2W until progression or toxicity. Primary endpoint: safety. Other endpoints: objective response rate (ORR), duration of response (DOR), OS. DOR and OS were assessed by Kaplan-Meier method. Results: Pts randomized to N3 + I1 and N1 + I3 cohorts were expanded to 47 pts per arm; N3 + I3 (n = 6) arm showed early toxicity and did not proceed to expansion. 53% and 47% of pts were treatment naive and previously treated in N3 + I1; 45% and 55% were in N1 + I3. Median (range) follow-up was 34.3 (15.4 – 80.1) wks in N3 + I1 and 31.3 (4.6 – 79.9) wks in N1 + I3. Treatment-related AEs were seen in 88% of pts. Discontinuations for any grade AE occurred in 16% of pts. Grade 3-4 treatment-related AEs occurred in 34% and 64% of pts in N3 + I1 and N1 + I3, respectively; most common: ↑ lipase (13% and 26%), ↑ ALT (4% and 19%), diarrhea (2% and 15%), colitis (0 and 13%), ↑ AST (4% and 9%), and ↑ amylase (4% and 9%). Most common grade 3-4 select AEs were GI and hepatic (N3 + I1, N1 + I3); GI: 2%, 23%; hepatic: 4%, 21%. Efficacy is summarized in the table below. Conclusions: Updated results from expanded cohorts in CheckMate 016 confirm initial safety findings and promising antitumor activity for N + I in pts with mRCC. OS results for N + I in mRCC appear encouraging and support further development of this combination in the first-line setting. Clinical trial information: NCT01472081. N3 + I1 n = 47 N1 + I3 n = 47 OS, mos (range) NR (3.5 – 18.4+) NR (1.1 – 18.4+) Overall ORRa, n (%) 18 (38) 20 (43) Stable disease, n (%) 19 (40) 18 (38) Median DORb, wks (range) NR (4.1+ – 67.1+) 53.9 (6.1+ – 66.0+) Median PFS, wks (range) 30.3 (4.7+ – 72.6+) 36.0 (4.1+ – 77.9+) PFS, 24 wks, % (95% CI) 53 (37 – 67) 64 (47 – 77) aConfirmed response + unconfirmed response; bConfirmed response. NR, not reached.