CheckMate 026: A phase 3 trial of nivolumab vs investigator's choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage iv/recurrent programmed death ligand 1 (PD-L1)−positive NSCLC

Background

Nivolumab improves OS compared with docetaxel in previously treated NSCLC. In a phase 1 study (CheckMate 012), nivolumab showed promising activity and manageable safety as monotherapy and in combination with ipilimumab in treatment naive advanced NSCLC. CheckMate 026 (NCT02041533), an open-label, randomized phase 3 study, evaluated the efficacy of nivolumab vs IC PT-DC as first-line therapy in stage IV/recurrent PD-L1–positive NSCLC.

Methods

Patients with histologically confirmed and previously untreated stage IV or recurrent NSCLC, ECOG PS 0–1, and PD-L1 positivity were randomized 1:1 to receive nivolumab 3 mg/kg IV Q2W or IC PT-DC (histology-based) Q3W (up to 6 cycles) until disease progression or unacceptable toxicity. Patients with EGFR/ALK mutations sensitive to targeted therapy were excluded. Patients on IC PT-DC could crossover to nivolumab upon progression. The primary objective was comparison of PFS (per RECIST 1.1) as assessed by an independent radiology review committee in patients with ≥5% PD–L1 tumor expression at randomization.

Results

A total of 541 patients were randomized to treatment. In patients with ≥5% PD-L1 expression (n = 423), nivolumab did not improve PFS (HR, 1.15; 95% CI 0.91 to 1.45; P = 0.25). Median PFS was 4.2 mo and 5.9 mo with nivolumab and IC PT-DC, respectively. Among all treated patients, any grade and grade 3/4 treatment-related adverse events were 71% and 18% with nivolumab, as compared to 92% and 51% with IC PT-DC, respectively. Secondary endpoints including PFS in all randomized patients, OS, and ORR will be presented.

Conclusions

Nivolumab did not show superior PFS compared to IC PT-DC as first-line therapy in stage IV/recurrent NSCLC patients with ≥5% PD-L1 tumor expression. The safety profile of nivolumab was favorable to IC PT-DC and consistent with previous studies. Nivolumab plus ipilimumab and nivolumab plus chemotherapy are being evaluated in a phase 3 trial in previously untreated NSCLC (CheckMate 227).

Clinical trial identification

NCT02041533

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

B. Creelan: Honoraria and research funding from Boehringer-Ingelheim. Received Speakers' Bureau payment and Travel, Accommodations, and Expenses from Bristol-Myers Squibb and AstraZeneca L. Horn: Consulting/Advisory Role with Genetech and Merck (compensated) & BMS, BI, Xcovery and Bayer (compensated). Research funding from AstraZeneca. Relationship with Biodesix. M. Reck: Consulting and Speakers' Bureau: Roche, Eli Lilly, Bristol Myers Squibb, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, Celgene. M. Steins: The author reports Honoraria and Consulting or Advisory Role for BMS. E. Felip: The author reports honoraria and consulting/advisory role with Boeheringer Ingelheim, MSD, Eli Lilly, Roche, Pfizer, Novartis, BMS, Celgene. The author reports Speakers Bureau for BMS, Novartis, Roche. T.E. Ciuleanu: The author reports advisory board work for Amgen, Astellas, AZ, BMS, Janssen, Lilly, Merck, Merck Sharp and Dohme. N. Ready: The author reports honoraria from BMS, Celgene, Heat Biologics and travel/accommodations/expenses from AZ. S. Nair: Received Research Funding from Bristol-Myers Squibb, Celldex—site PI for trials. R. Juergens: The author reports: Research Funding from AZ/MedImmune, BMS, Merck Sharp & Dohme, Novartis; Honoraria from Bayer, BMS, BI, BetaPharma, AZ, AZ/MedImmune, Roche Canada; Consulting /Advisory role for AZ, BI, BMS, Lilly, Novartis, Pfizer and Merck Sharp&Dohme. S. Peters: The author reports a consulting or advisory role with Roche, MSD, Lilly, Merck, Serono, Pfizer, AZ, Amgen, Celgene, BI, BMS. W.J. Geese: The author reports employment from BMS, stock or other ownership from BMS, and travel/accommodations/expenses from BMS. P. Bhagavatheeswaran, A. Chen: The author reports Employment and Stock or Other Ownership from BMS. D.P. Carbone: Writing Assistance provided by StemScientific, consulting for Genentech, Bristol Myers Squibb, Boehringer Ingelheim, Novartis, Pfizer, and Clovis (in the past but within the last 36 months). Grants from Bristol-Myers Squibb. All other authors have declared no conflicts of interest.