Therapeutic options for SCLC remain limited, with EP as the standard first-line chemotherapy regimen. However, patients (pts) with ES-SCLC experience high relapse rates within months after initial therapy. Pembrolizumab, a humanized monoclonal antibody against PD-1, has shown antitumor activity as monotherapy in heavily pretreated pts with PD-L1–positive SCLC in the phase 1b KEYNOTE-028 study. KEYNOTE-604 (ClinicalTrials.gov, NCT03066778) evaluates EP plus either pembrolizumab or placebo (pbo) as first-line therapy for ES-SCLC.
In this international, double-blind, phase 3 trial, adults with newly diagnosed ES-SCLC, ECOG PS ≤ 1, and no previous systemic therapy for SCLC are randomized 1:1 to receive either EP plus a 200-mg fixed dose of pembrolizumab intravenously (IV) once every 3 weeks (Q3W) or EP plus pbo IV Q3W. Randomization is stratified by the chosen platinum therapy (carboplatin vs cisplatin), ECOG PS (0 vs 1), and baseline lactate dehydrogenase concentration (≤ upper limit of normal [ULN] vs > ULN). Study treatment includes a total of 4 cycles of EP and 2 y of pembrolizumab/pbo and continues until documented PD, intolerable toxicity, or withdrawal of consent. Pts with a response after 4 cycles of EP plus pbo or pembrolizumab may receive prophylactic cranial irradiation. Pts who complete 2 y of pembrolizumab treatment or stop pembrolizumab for reasons other than PD/intolerability, but subsequently have documented PD, may receive an additional 1 y of pembrolizumab. Tumor response is assessed every 6 wk for 48 wk, and every 9 wk thereafter by RECIST version 1.1 by blinded independent central review. AEs occurring during treatment and 30 d thereafter (90 d for serious AEs) are graded per Common Terminology Criteria for Adverse Events, version 4.0. Primary endpoints are PFS and OS. Secondary endpoints are ORR, duration of response, safety, and patient-reported outcomes. Enrollment is ongoing with a planned enrollment of approximately 430 pts.
Clinical trial identification
NCT03066778; EudraCT Number: 2016-004309-15
Legal entity responsible for the study
Merck & Co., Inc., Kenilworth, NJ, USA
This research was supported by Merck & Co., Inc., Kenilworth, NJ, USA
C.M. Rudin: Advisory board member: Abbvie, Araxes, BMS, Celgene, G1 Therapeutics, Harpoon, Novartis. L. Shen, M.C. Pietanza: Employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA.