Tumors use the PD-1 pathway to suppress immune responses. The anti–PD-1 monoclonal antibody pembrolizumab (pembro) showed a manageable safety profile and promising antitumor activity in patients (pts) with treatment-naive NSCLC enrolled in the phase 1b KEYNOTE-001 study. KEYNOTE-042 (NCT02220894) is a randomized, open-label, international, phase 3 study comparing the efficacy and safety of pembro with those of platinum-doublet chemotherapy, the standard therapy for treatment-naive NSCLC lacking ALK translocations or EGFR-sensitizing mutations, as first-line therapy for PD-L1+ advanced NSCLC.
Pts with advanced NSCLC without EGFR-sensitizing mutations or ALK translocations and no prior systemic chemotherapy are eligible if they have PD-L1 expression in ≥1% of tumor cells and ECOG PS 0-1. Pts are randomized 1:1 to receive pembro 200 mg Q3W or investigator's choice of carboplatin AUC 5 or 6 + paclitaxel 200 mg/m2 Q3W or carboplatin AUC 5 or 6 + pemetrexed 500 mg/m2 Q3W. Randomization is stratified by ECOG PS (0 vs 1), histology (squamous vs nonsquamous), region (East Asia vs non-East Asia), and PD-L1 expression (staining in ≥50% of tumor cells [tumor proportion score (TPS) ≥50%] vs staining in 1%-49% of tumor cells [TPS 1%-49%] as assessed by IHC). Pembro will continue for 35 cycles or until progression, intolerable toxicity, or investigator decision; treatment may continue beyond initial radiographic disease progression in eligible pts. Discontinuation of pembro is permitted for pts who have CR confirmed ≥4 wk after initial observation. Chemotherapy will be given for a maximum of 6 cycles and may be followed by optional pemetrexed 500 mg/m2 Q3W maintenance therapy in pts with nonsquamous histology. AEs will be collected throughout the study and for 30 d (90 d for serious AEs) thereafter and graded per NCI CTCAE v4.0. Response will be assessed every 9 wk per RECIST v1.1 by central review. Pts will be followed for survival every 2 mo. Primary end point is OS in the PD-L1 TPS ≥50% stratum; secondary end points are PFS in the TPS ≥50% stratum and PFS and OS in all pts. Enrollment is ongoing and will continue until ∼1240 pts have enrolled.
Clinical trial identification
T. Mok: speaker/honoraria: AZ, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Amgen, Janssen, Clovis, GSK, Novartis; stock: Sanomics; Advisory board: AZ, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis, BioMarin, GSK, Novartis, SFJ. Y.-L. Wu: speaker fees: AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi. S. Sadowski, J. Zhang, R. Rangwala: employee of Merck & Co., Inc. G. de Lima Lopes: research/honoraria: Roche, Sanofi Aventis, Eli Lilly, Merck Serono, Merck Sharp & Dohme, BMS, Pfizer, Fresenius Kabi, AstraZeneca.