Nasopharyngeal carcinoma (NPC) exhibits high expression of PD-1, and expression of PD-1/PD-L1 correlated with poor outcome. Pembrolizumab is a potent, highly selective, humanized monoclonal antibody against PD-1 designed to block interaction with PD-L1 and PD-L2 and enhance antitumor immune response. We present results on safety and antitumor activity of pembrolizumab in patients (pts) with PD-L1+ advanced NPC.
KEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort, phase 1b trial of pembrolizumab in pts with PD-L1+ advanced solid tumors. Key eligibility criteria for the NPC cohort included advanced (unresectable and/or metastatic) solid tumor, failure of prior therapy, and PD-L1 expression in ≥1% of cells in tumor nests or PD-L1+ bands in stroma as determined by a prototype immunohistochemical assay at a central laboratory. Pembrolizumab 10 mg/kg was given every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points were safety, tolerability, and preliminary efficacy. Response was assessed per RECIST v1.1 by investigators every 8 weeks for the first 6 months and every 12 weeks thereafter.
27 pts were treated with pembrolizumab. Median (range) age was 52.0 (18-68) years; 63% were Asian. 92.5% received prior therapies for recurrent/metastatic disease (33.3% received ≥5 therapies). 7 pts experienced partial response and 14 had stable disease. Best overall (confirmed and unconfirmed) response rate was 25.9% (95% CI, 11.1-46.3). Most common adverse events (AEs) (≥20%) were fatigue (37.0%), pruritus (29.6%), nausea (25.9%), pyrexia (25.9%), and myalgia (22.2%). Drug-related AEs occurred in 74.1% of pts; most common (≥10%) were pruritus (25.9%), fatigue (18.5%), hypothyroidism (18.5%), rash (11.1%), maculopapular rash (11.1%), pneumonitis (11.1%), herpes zoster infection (11.1%), and hepatitis (11.1%); grade ≥3 drug-related AEs occurred in 8/27 (29.6%) pts. 5 pts remain on pembrolizumab treatment.
Pembrolizumab was well tolerated with significant antitumor activity in pts with NPC. This preliminary signal will be further investigated.
Clinical trial identification
J. Mehnert: Advisory board member for Amgen; research funding from Amgen, Novartis, Merck & Co., Inc., and Sanofi-aventis. A. Algazi: research funding from Merck & Co., Inc. S. Saraf: employee of Merck & Co., Inc. P. Thanigaimani: employee of Merck & Co., Inc. Owns stock in Gilead Sciences. J. Cheng: employee of and owns stock in Merck & Co., Inc. All other authors have declared no conflicts of interest.