HB-200 arenavirus-based immunotherapy plus pembrolizumab as first-line treatment of patients with recurrent/metastatic HPV16-positive head and neck cancer: Updated results.
Authors: Alan Loh Ho, Lisle Nabell, Prakash C. Neupane, Marshall R. Posner, Emrullah Yilmaz, Jiaxin Niu, Abdul Rafeh Naqash, Alexander T. Pearson, Stuart J. Wong, Jorge J. Nieva, Douglas Earl Laux, Deborah J.L. Wong, Zujun Li, Ari Joseph Rosenberg, Winston Wong, Xiaoping Qing, Corinne Iacobucci, Henning Lauterbach, Ilian Tchakov, David G. Pfister
Journal: Journal of Clinical Oncology (2024)

6005 Background: Treatment options are limited for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with no approved treatment specifically targeting human papillomavirus (HPV) 16-positive tumors. In the first-line (1L) R/M setting, only a minority of patients (~20%) respond to pembrolizumab monotherapy, including those with high programmed death ligand 1 (PD-L1) expression in the tumor. HB-200 comprises an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively. HB-200 vectors express a non-oncogenic HPV16 E7E6 fusion protein and induce E6 and E7-specific CD8 T-cell responses. Previously, we reported promising preliminary clinical activity of HB-200 in combination with pembrolizumab as 1L treatment for patients with HPV16+ PD-L1+ R/M HNSCC. Here, we report updated results with a focus on PD-L1 status. Methods: In this non-randomized Phase 2 part of the study, participants with HPV16+ PD-L1 combined positive score (CPS) ≥1 R/M HNSCC were treated with HB-200 intravenously (every 3 weeks [Q3W] then Q6W) in combination with pembrolizumab (200 mg Q3W or 400 mg Q6W). Safety, T cell response, and preliminary antitumor activity were assessed. Results: As of 12 January 2024, 42 patients with HPV16+ PD-L1+ R/M HNSCC (41 of oropharynx as primary cancer site) were treated with HB-200 plus pembrolizumab in the 1L setting. Median follow-up time was 5.6 months. Characteristics of this cohort included: median age 66 years (range 50-77), 41 (98%) male, 37 (88%) White, 14 (33%) with ≥ 10 pack/year smoking history, 40 (95%) check point inhibitor (CPI) naïve (2 received CPI in the adjuvant setting), and 21 (50%) with PD-L1 CPS ≥ 20. HB-200 + pembrolizumab were generally well tolerated. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 6 (14%) patients, serious TRAEs in 3 (7%) patients, and TRAEs leading to treatment discontinuation in 2 (5%) patients. No treatment-related death were reported. Among 35 evaluable patients (those with ≥ 1 tumor response assessments), the overall response rate (ORR) was 43% (3 complete response [CR], 9 partial response [PR], 3 unconfirmed PR) and the disease control rate (DCR) was 71%. Notably, among patients with PD-L1 CPS ≥20 (N = 17), ORR was 59% (3 CR, 6 PR, 1 unconfirmed PR) and DCR was 88%. Conclusions: Updated data of HB-200 arenavirus-based immunotherapy plus pembrolizumab continued to demonstrate a favorable safety profile and promising clinical activity as 1L treatment in patients with HPV16+ PD-L1+ R/M HNSCC and confirms previously reported data. The results suggest that the subgroup of patients with PD-L1 CPS ≥20 may benefit more from this treatment, which warrants further development in a randomized pivotal study. Clinical trial# NCT04180215. Clinical trial information: NCT04180215 .