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Program Number: AHNS13
Session Name: Scientific Session 3 - Immunotherapy
Session Date: Wednesday, May 14, 2025
Session Time: 3:15 PM - 4:00 PM

A Phase 2, Open-Label Study of Intratumoral Vidutolimod in Combination With Intravenous Pembrolizumab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Deborah J Wong¹; Lori Wirth²; Douglas Laux³; Ammar Sukari⁴; Mirabelle Sajisevi⁵; Dan Paul Zandberg⁶; Assuntina Sacco⁷; Jacob Thomas⁸; Aru Panwar⁹; Jun Zhang¹⁰; Robert Siegel¹¹; Mia Bao¹²; Jocelyn Booth¹²; Christy French¹²; Israel Lowy¹²; Matthew Fury¹²; Mihaela Cristea¹²; ¹University of California Los Angeles Medical Center; ²Massachusetts General Hospital; ³University of Iowa Hospitals & Clinics; ⁴Karmanos Cancer Institute; ⁵University of Vermont Medical Center; ⁶University of Pittsburgh Medical Center - Hillman Cancer Center; ⁷University of California, San Diego; ⁸University of Southern California; ⁹Nebraska Methodist Hospital; ¹⁰Houston Methodist Hospital; ¹¹St. Francis Cancer Center; ¹²Regeneron Pharmaceuticals, Inc.

Background: The programmed cell death 1 (PD-1) inhibitor pembrolizumab ± chemotherapy is recommended as 1L treatment for patients with recurrent, unresectable, or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, most do not respond, indicating an unmet need for patients with unresectable disease. The toll-like receptor 9 agonist vidutolimod (CMP-001) is a CpG-A oligodeoxynucleotide encapsulated within a noninfectious virus-like particle. Vidutolimod activates tumor-associated plasmacytoid dendritic cells, triggering type I interferon secretion that enhances antitumor T-cell response. This phase 2 study evaluated vidutolimod plus pembrolizumab in patients with R/M HNSCC (NCT04633278).

Study Design and Methods: This multicenter, open-label study assessed intratumoral (IT) injection of vidutolimod plus intravenous (IV) pembrolizumab in PD-1 inhibitor-naive patients with R/M HNSCC whose tumors had a programmed death-ligand 1 combined positive score (CPS) of ≥1. In Schedule A, patients received vidutolimod 10 mg IT once weekly for 7 doses, then Q3W plus pembrolizumab 200 mg IV at Week 1 Day 1 and Q3W thereafter. In Schedule B, patients received vidutolimod 10 mg IT once weekly for 2 doses, then Q3W plus pembrolizumab 200 mg IV starting from the second dose of pembrolizumab at Week 4 Day 1. Treatment continued until discontinuation conditions were met or up to 2 years. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included safety, duration of response, progression-free survival (PFS), and overall survival (OS).  

Results: Twenty-four patients received vidutolimod plus pembrolizumab and were included in the analysis. For patients in the combined schedules (N=24), median age was 66.0 years (range, 46-86); the most frequent primary sites of HNSCC were oral cavity (38% [9/24]) and oropharynx (33% [8/24]); 50% had a CPS of 1%-19% and 46% had a CPS of ≥20%; and 7 of 16 tested were HPV positive (6 oropharynx; 1 oral cavity). Median time on study was 5.4 months (range, 1-28). Confirmed ORR for patients in the combined schedules was 12.5% (95% CI, 2.66-32.36), which included 3 partial responses (PRs) all in Schedule A. Two PRs occurred in patients with tumors exhibiting CPS <20 and 1 PR occurred in a patient with CPS ≥20. Two of the 3 PR patients experienced durable disease stabilization (>22 months). An HPV-positive oropharynx patient had a durable PR (18 months), and 1 had a near PR (–29%). In the combined schedules, median PFS was 2 months (95% CI, 1.64-3.98), and median OS was 6.93 months (95% CI, 2.66-12.29). The table shows efficacy for Schedules A and B. All patients had ≥1 treatment-emergent adverse event (TEAE), including 54% grade 3 (13/24) and 4% grade 5 (1/24) TEAEs. The most frequent any-grade TEAEs (in ≥20%) were chills (46% [11/24]), pyrexia (33% [8/24]), constipation (29% [7/24]), nausea and hypotension (25% each [6/24]), and fatigue, headache, and hypothyroidism (21% each [5/24]). Three (13%) patients experienced TEAEs that led to study discontinuation for vidutolimod and two (8%) for pembrolizumab.

Conclusion: Vidutolimod plus pembrolizumab had a generally manageable safety profile and demonstrated durable disease control among responders in PD-1 inhibitor-naive patients with R/M HNSCC.

 

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