Pembrolizumab in combination with ipilimumab as second-line or later therapy for advanced non-small-cell lung cancer: KEYNOTE-021 cohorts D and H.

摘要: Abstract Objectives Combination immunotherapy may result in improved antitumor activity compared with single-agent treatment. We report results from dose-finding and dose-expansion cohorts of the phase 1/2 KEYNOTE-021 study that evaluated combination therapy anti‒programmed death 1 (PD-1) antibody pembrolizumab plus anti‒cytotoxic T-lymphocyte antigen-4 (CTLA-4) ipilimumab patients previously treated advanced non–small-cell lung cancer (NSCLC). Materials methods Eligibility criteria stipulated histologically/cytologically confirmed NSCLC treatment failure on ≥1 prior systemic (platinum-based chemotherapy or targeted for EGFR/ALK aberrations). In cohort, initially received 10 mg/kg 3 mg/kg once every 3 weeks 4 cycles followed by monotherapy up to 2 years. Based emerging published data, subsequent 2 mg/kg 1 mg/kg. Objective response rate (ORR; primary efficacy endpoint) was assessed per RECIST version 1.1 blinded, independent central review. Phase hypothesis ORR would be greater than 20% historical controls using exact binomial test. Results Fifty-one were enrolled; 71% ≥2 lines therapy. No dose-limiting toxicities occurred at any dose level. Among who 1 mg/kg (n = 44), 30% (95% CI, 17%–45%), but not statistically significantly >20% (P = 0.0858). Median progression-free survival this group 4.1 1.4–5.8) months; median overall 10.9 6.1–23.7) months. With mg/kg mg/kg, incidences treatment-related adverse events, grade 3–5 immune-mediated events infusion reactions 64%, 29%, 42%, respectively. Conclusions heavily pretreated NSCLC, showed evidence activity, associated meaningful toxicity.