KEYNOTE-033: Phase 3 study of pembrolizumab versus docetaxel in patients with previously treated non–small-cell lung cancer (NSCLC)

Background: Docetaxel is widely used in China as second-line therapy for advanced NSCLC, with an objective response rate (ORR) of 5%–10% and median progression-free survival (PFS) and overall survival (OS) of ∼3 and ∼7.5 months, respectively. In KEYNOTE-010, treatment with the humanized anti–PD-1 monoclonal antibody pembrolizumab significantly improved OS as second-line or later therapy in patients with advanced NSCLC expressing PD-L1. KEYNOTE-033 is a randomized open-label study comparing the efficacy and safety of pembrolizumab monotherapy with standard-of-care docetaxel monotherapy in patients (majority from China) with previously treated PD-L1–positive NSCLC. Trial design: Eligible patients in this phase 3 study are aged ≥18 years with confirmed stage III/IV or recurrent PD-L1–positive (tumor proportion score [TPS] ≥1%) NSCLC, with disease progression after ≥1 line of platinum-containing doublet therapy. Patients with tumors with EGFR-sensitizing mutations are excluded and those with ALK translocations must have disease progression on both platinum-containing doublet and ALK-directed tyrosine kinase inhibitor therapy. ∼740 eligible patients will be randomized 1:1 to receive pembrolizumab 2 mg/kg Q3W or docetaxel 75 mg/m2 Q3W. Treatment will be administered for 2 years/35 cycles (whichever is later), or until disease progression, intolerable toxicity, or withdrawal of consent. Randomization will be stratified by PD-L1 TPS (≥50% vs < 50%). Tumor response will be evaluated Q9W by RECIST v1.1 by blinded independent central review. Adverse events occurring during the study will be graded using NCI CTCAE v4.0. Primary endpoints are OS and PFS. Secondary endpoints include ORR and duration of response. Patient-reported outcomes are an exploratory objective. Enrollment has been initiated; 52 sites are planned including 25 in mainland China and others in Argentina, Philippines, Taiwan, Thailand, Mexico, Chile and Ukraine. Clinical trial indentification: ClinicalTrials.gov, NCT02864394. Legal entity responsible for the study: This research was supported by Merck & Co., Inc., Kenilworth, NJ, USA Funding: This research was supported by Merck & Co., Inc., Kenilworth, NJ, USA Disclosure: C. Zhou: Lecture honoraria: Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Sanofi Research Funding: Pfizer, Boehringer Ingelheim, C. Caglevic: Speaker: BMS, MSD, Boehringer Ingelheim, Tecnofarma Advisory and Consulting: BMS, MSD, Boehringer Ingelheim, Eli Lilly, AstraZeneca, Bayer Investigator: MSD, BMS, Boehringer Ingelheim, Bayer, Roche, Astra Zeneca, Astellas, Advaxis Acommodation Grants: Boehringer Ingelheim, J. Ge, Y. Zhou: Employment: MSD China, Shanghai, CN, B. Piperdi: Employment: Merck & Co., Inc., Kenilworth, NJ, US All other authors have declared no conflicts of interest.