KEYNOTE-122: Phase 2 study of pembrolizumab versus standard-of-care chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal carcinoma

Abstract

BACKGROUND: Current treatment for recurrent/metastatic nasopharyngeal carcinoma (NPC) that progresses on a platinum-based regimen is limited. Prolonged exposure to Epstein-Barr virus (EBV) in NPC leads to increased expression of programmed death 1 (PD-1), resulting in suppressed T-cell immunity and tumor surveillance. Pembrolizumab is a monoclonal anti–PD-1 antibody designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. In the phase 1b KEYNOTE-028 study, pembrolizumab was associated with an overall response rate of 22% (6/27) in mostly heavily pretreated patients with NPC. KEYNOTE-122 (NCT02611960) is a multicenter, open-label, randomized phase 2 study designed to evaluate the efficacy and safety of pembrolizumab monotherapy versus chemotherapy in patients with platinum-pretreated, recurrent or metastatic NPC. TRIAL DESIGN: Key eligibility criteria include age ≥18 years, histologically confirmed nonkeratinizing differentiated NPC (WHO Class II) or undifferentiated NPC (WHO Class III), metastatic or recurrent disease, EBV positivity determined locally or centrally by EBV-encoded small RNA in situ hybridization, previous treatment with platinum-containing regimen, ECOG performance status 0-1, and measurable disease per RECIST v1.1. Patients will be randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 weeks (Q3W) or investigator’s choice of chemotherapy (capecitabine 1000 mg/m2 twice daily on days 1-14 of each 3-week cycle, gemcitabine 1250 mg/m2 once per week on days 1 and 8 of each 3-week cycle, or docetaxel 75 mg/m2 Q3W). Treatment will continue until disease progression, unacceptable toxicity, investigator decision, or 35 cycles of pembrolizumab. Response will be evaluated every 6 weeks for the first year of treatment and every 9 weeks thereafter per RECIST v1.1 by central imaging assessment. Primary end points are overall survival and progression-free survival per RECIST v1.1 by central imaging assessment; secondary end points include objective response rate and duration of response. Enrollment is ongoing and will continue until approximately 160 patients have enrolled.