Abstract 972TiP
Background
MK-1454, an investigational cyclic dinucleotide stimulator of interferon genes (STING) agonist, in combination with pembrolizumab (pembro), an anti–PD-1 antibody, produced encouraging efficacy with an acceptable safety profile in a phase I study in patients with solid tumors or lymphomas. In KEYNOTE-048, which compared pembro ± chemotherapy with cetuximab + chemotherapy in patients with previously untreated metastatic or recurrent head and neck squamous cell carcinoma (HNSCC), pembro significantly prolonged OS as monotherapy in patients with a PD-L1 combined positive score (CPS) ≥1 and ≥20 and in combination with chemotherapy in patients with CPS ≥1 and ≥20 and in the total population. This phase II study (NCT04220866) is evaluating intratumoral MK-1454 + pembro or pembro as first-line treatment for metastatic or recurrent HNSCC.
Trial design
This open-label study is enrolling patients with histologically or cytologically confirmed metastatic or unresectable, recurrent HNSCC that is considered incurable by local therapies. Patients must have ≥1 measurable lesion amenable to injection, PD-L1 CPS ≥1, and ECOG PS 0 or 1. Approximately 200 patients (target) will be randomized (1:1) to intratumoral MK-1454 540 μg (Q1W for 6 cycles then Q3W) in combination with intravenous pembro 200 mg (Q3W) or pembro alone for up to 35 cycles, with stratification by PD-L1 status (CPS ≥1–<20 vs ≥20), ECOG PS (0 vs 1), and human papilloma-virus status (positive vs negative). The primary efficacy endpoint, ORR (blinded independent central review, RECIST version 1.1), will be analyzed using the stratified Miettinen and Nurminen method, testing the dual primary hypotheses that MK-1454 + pembro produces a superior ORR vs pembro alone in patients with CPS ≥1 and CPS ≥20. Type I error rate will be controlled at α=1% for CPS ≥1 and α=1.5% for CPS ≥20. Secondary endpoints include PFS, duration of response, and OS. Safety and tolerability are assessed based on AEs (NCI CTCAE version 5.0), laboratory tests, vital signs, and electrocardiograms. Enrollment is ongoing.
Clinical trial identification
2019-003060-42; NCT04220866.
Editorial acknowledgement
Writing support was provided by Nicole Strangman, PhD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
K.J. Harrington: Honoraria (self): AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck-Serono, MSD, Oncolys, Pfizer, Replimune; Advisory/Consultancy: AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck-Serono, MSD, Oncolys, Pfizer, Replimune; Research grant/Funding (institution): AstraZeneca, Boehringer-Ingelheim, MSD, Replimune. W.N. William Jr.: Speaker Bureau/Expert testimony, received speaker fees: BMS, Merck, Roche / Genentech, AstraZeneca, Pfizer, Boehringer Ingelheim, Bayer; Honoraria (self), received honoraria: BMS, Merck, Roche / Genentech, AstraZeneca, Pfizer, Boehringer Ingelheim, Bayer. A. Khilnani: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.A.P. Algazi: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Shareholder/Stockholder/Stock options, research support, advisory board member, consultant, shareholder, honorarium: OncoSec; Advisory/Consultancy, Shareholder/Stockholder/Stock options, advisory board member, stock shareholder: Valitor Biosciences; Honoraria (self), Advisory/Consultancy: Regeneron, Array; Research grant/Funding (institution): Acerta, Amgen, AstraZeneca, Bristol-Myers Squibb, Dynavax, Genentech, Idera, Incyte, ISA, LOXO, Merck, Novartis, Sensei, Tessa.