First report of the safety/tolerability and preliminary antitumor activity of HB-201 and HB-202, an arenavirus-based cancer immunotherapy, in patients with HPV16+ cancers.
Authors: Alan Loh Ho, Marshall R. Posner, Jiaxin Niu, Siqing Fu, Rom S. Leidner, Alexander T. Pearson, Ki Y. Chung, Debra L. Richardson, Ding Wang, Agustin Pimentel, Jorge J. Nieva, Ari Rosenberg, Bharat Burman, Corinne Iacobucci, Xiaoping Qing, Andy Hwang, Kia Katchar, Katia Schlienger, Igor Matushansky, David G. Pfister
Journal: Journal of Clinical Oncology (2021)

2502 Background: Human papillomavirus 16 (HPV16) is linked to several cancer types. Treatment options are limited for patients with HPV16 positive (HPV16+) recurrent or metastatic cancers. Generation and maintenance of HPV16+ malignant state require stable expression of HPV16-specific E7 and E6 oncoproteins, also a source of immunogenic neoantigens. HB-201 and HB-202 are replicating live-attenuated vectors based on lymphocytic choriomeningitis virus and Pichinde virus, respectively, which express the same non-oncogenic HPV16 E7E6 fusion protein to induce tumor-specific T-cell responses. This is a first-in-human phase 1/2 study of HB-201 monotherapy and HB-201 &amp; HB-202 alternating 2-vector therapy. Dose escalation is ongoing with a 3+3 design. Methods: Phase 1 is assessing different regimens and dose levels of HB-201 monotherapy and HB-201 &amp; HB-202 alternating 2-vector therapy given intravenously (IV) with or without an initial intratumoral administration. The patient population includes HPV16+ head and neck squamous cell carcinoma (HNSCC) and other HPV16+ cancers. Safety, tolerability, and preliminary antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or immune RECIST are assessed. Results: As of Jan 2021, 25 patients with a median of 3 prior anticancer treatments have been enrolled. All had HPV16+ confirmed genotype; the most common primary site was oropharynx (72%). No dose-limiting toxicities were reported. Treatment-emergent adverse events (TEAEs) occurred in 21 patients (84%), were generally mild or moderate, with events related to study drug reported in 14 patients (56%). TEAEs reported in &gt;10% of patients regardless of causality included fatigue, pyrexia, nausea, decreased appetite, anemia, arthralgia, chills, constipation, diarrhea, hypertension, influenza-like illness, pneumonia, and vomiting. Serious TEAEs developed in 6 patients (24%), including 1 with grade 5 hemorrhagic shock deemed unrelated to study drug. Grade 3 fatigue was the only serious or grade ≥3 TEAE assessed as related to study drug. TEAEs caused no treatment discontinuation. There were 18 patients evaluable for efficacy. For the 16 patients on HB-201 monotherapy, assessment of target lesions showed 2 partial responses (including 1 patient with an unconfirmed immune CR) and 6 patients had stable disease (SD). For the 2 patients on HB-201 &amp; HB-202 alternating therapy, both had SD. So far, the longest duration of response was 4.8 months (144 days) and the maximum decrease in tumor diameter was 60%, both seen in HNSCC patients receiving HB-201 IV. Conclusions: HB-201 monotherapy and HB-201 &amp; HB-202 2-vector alternating therapy were generally well-tolerated and showed preliminary antitumor activity as monotherapy in heavily pre-treated patients with HPV16+ HNSCC and other solid tumors. Clinical trial information: NCT04180215.