CheckMate 012: Safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC.
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.3001
ISSN1527-7755
AutoresMatthew D. Hellmann, Scott Gettinger, Jonathan W. Goldman, Julie R. Brahmer, Hossein Borghaei, Laura Q.M. Chow, Neal Ready, David E. Gerber, Rosalyn A. Juergens, Frances A. Shepherd, Scott A. Laurie, Ye Zhou, William J. Geese, Shruti Agrawal, Xuemei Li, Scott Antonia,
Tópico(s)Cancer Genomics and Diagnostics
Resumo3001 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.
Referência(s)