A Phase Ib Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Human Papiilloma Virus (Hpv)-Positive and Negative Head and Neck Cancer (Hnc)

Abstract

ABSTRACT Aim: Background: The highly selective, anti-PD-1 humanized monoclonal antibody pembro has shown antitumor activity in several solid tumors, including HNC. We present updated safety, tolerability, and antitumor activity of pembro for recurrent/metastatic HNC (Clinicaltrials.gov: NCT01848834). Methods: During screening, PD-L1 expression in archival or newly obtained tumor samples was assessed using a prototype immunohistochemistry assay; PD-L1 expression in stroma or ≥1% of tumor cells was required for study entry. Pembro 10 mg/kg was given every 2 wk until complete response, progression, unacceptable toxicity, physician decision, or consent withdrawal. Adverse events (AEs) were recorded throughout the study. Response was assessed every 8 wk. Primary end point was overall response rate (ORR) per RECIST v1.1. Results: Out of 104 HNC pts screened, 81 (78%) were PD-L1-positive, 61 enrolled, and 60 received ≥1 pembro dose: 23 HPV+, 37 HPV-. After a median follow-up of 10.2 mo, 15 pts (25%) remain on pembro. ORR (confirmed + unconfirmed) per RECIST v1.1 by investigator review was 20%, and response duration ranged from 8+ to 41+ weeks (median not reached). 9 of 11 responders had a smaller target lesion burden (ie, sum below the median) at baseline. ORR was similar in HPV+ and HPV- pts, whereas PFS and OS were longer in HPV+ pts (Table). PD-L1 expression was positively correlated with ORR (P = 0.018) and PFS (P = 0.024). ORR was 50% in the 12 pts with high PD-L1 expression. Drug-related AEs of any grade occurred in 58% of pts (grade ≥3 in 17%). The most common drug-related AEs were fatigue (18%), pruritus (10%), and nausea (8%). There were no drug-related deaths. Conclusions: Pembro is safe and tolerable and shows antitumor activity in both HPV+ and HPV- advanced HNC. These findings support further development of pembro in advanced HNC. Overall N = 61* HPV+ n = 23* HPV– n = 38* ORR, n (%) 11 (20) 4 (20) 7 (19) Median PFS (95% CI), wk 9.3 (8.0-20.1) 17.2 (8.0-41.7) 8.1 (7.9-15.6) Median OS (95% CI), mo 12.6 (8.2-12.6) NR (9.6-NR) 9.5 (3.9-12.6) *ORR and PFS were evaluated in the 56 pts (20 HPV+, 36 HPV-) who received ≥1 pembro dose and had measurable disease per RECIST v1.1 by investigator review. Disclosure: L.Q. Chow: Advisory Board Member for Bristol Myers Squibb, Novartis, Celgene; Research funding from Bristol Myers Squibb, Novartis, AstraZeneca/Medimmune, Genentech/Roche, VentiRx, Pfizer, Lily/Imclone; B. Burtness: Advisory board membership for VentiRx and Novartis; Research funding from Merck, Genentech, Boehringer Ingelheim, and Pfizer; E.J. Gonzalez, J.K. Lunceford, C. Gause and J.D. Cheng: Employee of and stock ownership in Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.; J. Pulini, J. Johnson, M. Dolled-Filhart, K. Emancipator and K. Pathiraja: Employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.; T. Seiwert: Advisory board membership for Novartis and Onyx/Bayer; Research funding from Boehringer Ingelheim and Genentech; Honoraria from Merck. All other authors have declared no conflicts of interest.