CheckMate 012: Safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC.

Abstract

3001 Background: Nivo + ipi is approved in adv melanoma and has demonstrated clinical activity and manageable safety in various solid tumors. CheckMate 012 is a phase I study of nivo monotherapy or combined with other therapies in 1L adv NSCLC; we report updated results, including tumor growth dynamic (TGD) modeling, from N+I dosing schedules explored to optimize safety and permit synergistic activity. Methods: Patients ([pts] N=148, any NSCLC histology) received N+I (mg/kg) across 4 dose cohorts (Table). Primary objective was safety; secondary objectives were ORR (RECIST v1.1) and 24-wk PFS rate; exploratory endpoints were OS and efficacy by tumor programmed death ligand 1 (PD-L1) expression. The effect of N+I dosing was assessed by TGD modeling generated using individual tumor assessments; model-predicted tumor shrinkage at wk 12 was compared across cohorts. Results: Treatment-related (TR) adverse events (AEs) and select TRAEs were manageable (Table). TRAEs leading to discontinuation (DC) were comparable to nivo alone (10%), with no TR deaths. Across cohorts, ORRs ranged from 13%–39% (Table), and median duration of response was not reached. Responses were noted regardless of PD-L1 expression, with a higher magnitude of benefit in tumors that expressed PD-L1. TGD modeling predicted enhanced tumor shrinkage for N3 + I1 schedules compared with nivo alone or any N1-containing schedule. Based on integrated efficacy/safety/TGD data, N3 Q2W + I1 Q6W was proposed for further evaluation. Conclusions: 1L therapy with N+I demonstrates clinical activity and a manageable safety profile. Updated safety and efficacy across cohorts (by histology, EGFR, smoking status, PD-L1 expression) and TGD modeling data will be presented. Clinical trial information: NCT01454102. N1 + I1 Q3W x 4 cycles, then N3 Q2W (n=31) N1 Q2W + I1 Q6W (n=40) N3 Q2W + I1 Q12W (n=38) N3 Q2W + I1 Q6W (n=39) TRAEs, % Any gr 77 73 74 69 Gr 3–4 29 35 29 28 Select TRAEs, gr 3–4, % Skin 13 5 3 5 Gastrointestinal 0 8 5 5 Endocrine 6 8 3 5 Hepatic 6 10 0 5 Pulmonary 3 0 3 3 Renal 0 0 5 0 Hypersensitivity/Infusion 0 0 0 0 TRAEs leading to DC, % 13 8 5 10 ORR, % 13 25 39 31 mPFS, mo 10.6 4.9 8.0 8.3 24-wk PFS rate, % 55 NC 63 NC Median follow-up, mo 16.6 6.2 8.4 7.7 NC = not calculated; Gr = grade.