Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study

Abstract

Objectives: Treatment options for patients with unresectable or metastatic salivary gland carcinoma (SGC) are limited. Safety and efficacy of pembrolizumab for SGC expressing programmed death ligand 1 (PD-L1) were explored.

Materials and methods: A cohort of patients with advanced, PD-L1-positive SGC was enrolled in the nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors (KEYNOTE-028; NCT02054806). Key inclusion criteria included recurrent or metastatic disease, failure of prior systemic therapy, and PD-L1 expression on ≥1% of tumor or stroma cells (per a prototype immunohistochemistry assay). Patients received pembrolizumab 10 mg/kg every 2 weeks for ≥2 years or until confirmed disease progression or unacceptable toxicity. Primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator review.

Results: Twenty-six patients with PD-L1-positive SGC were enrolled and treated; median age was 57 years, 88% were men, and 74% had received prior therapy for recurrent/metastatic disease. Confirmed objective response rate after median follow-up of 20 months was 12% (95% confidence interval, 2%-30%), with 3 patients achieving partial response; there were no complete responses. Median duration of response was 4 months (range, 4 to 21 mo). Treatment-related adverse events occurred in 22 patients (85%), resulting in discontinuation in 2 patients and death in 1 (interstitial lung disease); those occurring in ≥15% of patients were diarrhea, decreased appetite, pruritus, and fatigue.

Conclusions: Pembrolizumab demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, PD-L1-positive SGC.

Conflict of interest statement

R.B.C. received a research grant from Merck & Co. Inc., paid to the University of Pennsylvania and was a member of an advisory board for Bristol-Myers Squibb. T.D. received research funding from Taiho, Novartis, Merck Serono, Astellas Pharma, Merck & Co. Inc., Janssen, Boehringer Ingelheim, Takeda, Pfizer, Eli Lilly Sumitomo Group, Chugai Pharma, Bayer, Kyowa Hakko Kirin, Daiichi Sankyo, Celgene, and Amgen. S.A.P. received research funding to the institution from the National Institutes of Health (grant number P30CA016672). S.V.L. was a member of an advisory board for Genentech, Boehringer Ingelheim, Celgene, Ariad, and Pfizer. J.G. received a research grant paid to the institution from Merck & Co. Inc., AstraZeneca, Novartis, Bristol-Myers Squibb, Karyopharm, and Pfizer. A.P.A. received a research grant from Merck & Co. Inc., paid to the institution. C.L. was a member of an advisory board for Merck & Co. Inc. S.S., J.C. are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ. P.T. is currently an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, and was previously an employee of Boehringer Ingelheim, from May 2012 to August 2014, and owned stock in Gilead from June 2014 to June 2016. J.P.D., S.D., R-L.H., D.D., A.V., E.E., J.W., B.K. declare no conflicts of interest.

Figures

FIGURE 1

Treatment exposure to pembrolizumab and summary of best overall response assessed per RECIST by investigator review (N=26). Patients with radiographic progression who were clinically stable or clinically improved, with no further evidence of RECIST progression on subsequent scans could continue treatment after consultation with the sponsor and at the investigator’s discretion. PD indicates progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors version 1.1.

FIGURE 2

Waterfall plot of best percentage change from baseline (A) and percentage change from baseline in the sum of the longest diameters of target lesions (B) as assessed per Response Evaluation Criteria in Solid Tumors by investigator review (N=26).

FIGURE 3

Kaplan-Meier estimates of (A) progression-free survival per Response Evaluation Criteria in Solid Tumors by investigator review and (B) overall survival (N=26).