Posner MR, Ho AL, Niu J, Nabell L, Leidner RS, Nieva J, Richardson DL, Pearson AT, Wang D, Chung K, Adkins DR, Pimentel A, Wong S, Lacobucci C, Qing X, Katchar K, Schlienger K, Matushansky I, Fu S, and Pfister DG. 961MO Safety, efficacy, immunogenicity of arenavirus-based vectors HB-201 and HB-202 in patients with HPV16+ cancers. Ann Oncol 2021; 32:S831-S832.
Background: Human papillomavirus 16 positive (HPV16+) cancers are caused by stable expression of HPV16-specific E7 and E6 oncoproteins, also a source of immunogenic neoantigens. Replicating arenavirus vectors HB-201 (LCMV) and HB-202 (Pichinde virus), expressing the same non-oncogenic HPV16 E7E6 fusion protein, induce tumour-specific T-cell responses.
Methods: A phase I first-in-human study assessed HB-201 monotherapy and HB-201 & HB-202 alternating 2-vector therapy (HB-201/HB-202) intravenously (IV) with or without 1 intratumoral dose (IT/IV) in HPV16+ cancers. Safety, tolerability, and preliminary anti-tumour activity by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or immune RECIST were evaluated, as well as immunogenicity and pharmacodynamic biomarkers in blood and tumour tissue samples.
Results: The study treated 38 patients (29 with ≥1 efficacy scan) with confirmed HPV16+ cancers with a median (range) of 3 (1e10) prior anticancer therapies. The most common primary cancer site was oropharynx (76%), followed by cervical (7.9%). Eighteen patients received HB-201 monotherapy IV and 9 IT/IV; 11 patients received HB-201/HB-202 alternating therapy. Treatment was generally well tolerated. Twenty patients (53%) reported treatment-related adverse events (all Grade 2). Two of 11 evaluable patients treated with HB-201 IV every 3 weeks had partial response (including 1 unconfirmed immune complete response of target lesion) and 6 had stable disease (SD) lasting 1.2e5.9 months. All 6 evaluable patients that received HB201/HB-202 had SD. HPV16-specific T-cells in peripheral blood were detected at several time points post-administration through direct ex vivo stimulation. Different schedules, regimens, modes of administration, and doses will be presented with corresponding immunogenicity data. The proposed pathway to the recommended phase II regimen will be discussed.
Conclusions: Arenavirus-based vectors HB-201 and HB-201/HB-202 appeared well tolerated and showed preliminary anti-tumour activity as single agents in this heavily pretreated population of patients with HPV16+ cancers. Induction of circulating E7E6- specific activated CD8+ T-cells was observed.
Clinical trial identification: NCT04180215.