Phase II multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy of HB-200 in patients with detectable TTMV-HPV DNA after definitive treatment for HPV16 + HNSCC

BackgroundSurveillance for HNSCC recurrence after definitive therapy relies on regular clinical exams. The NavDx assay (Naveris Inc.) detects circulating tumor tissue modified viral (TTMV)-HPV DNA and has shown the ability to identify recurrence in patients (pts) prior to emergence of clinical or radiographic disease. The positive predictive value for clinical recurrence by NavDx testing performed 3 months after definitive therapy is 95-98% based on prior studies. This minimal residual disease (MRD) state with positive TTMV DNA (NavDx) prior to evident structural disease, is a novel and untested clinical setting in which early intervention may delay or eradicate recurrent cancer in pts. HB-200 is an arenavirus based vaccine therapy that stimulates an E6/E7 antigen specific anti-tumor immune response, and has demonstrated promising preliminary efficacy in the recurrent/metastatic setting. This study seeks to evaluate HB-200 as treatment for MRD evident by NavDx after definitive treatment for HNSCC.Trial designThis is a multi-centered, randomized, double-blind, placebo-controlled Phase II study at Memorial Sloan Kettering and additional sites. Planned enrollment is n=51 pts. Pts will be randomized to treatment with HB-200 or placebo in a 2:1 fashion. Enrollment requirements include a detectable TTMV-HPV DNA > 3 months after definitive treatment for HPV16+ HNSCC and no clinical/radiographic evidence of disease prior to or at time of enrollment. Alternating IV HB-202 and HB-201 (HB-200) treatment will be given on a Q3W schedule for 5 doses prior to transitioning to a Q6W schedule and continued until radiographic or clinical recurrence or for a total of 1 year of treatment. Pts in the placebo group will be given IV placebo on the same schedule for a total of 1 year. Recurrence will be defined as those with development of tumor/disease detected radiographically or clinically that is pathologically confirmed. The primary objective is to assess the disease-free survival (DFS) for pts enrolled in the study receiving either HB-200 or placebo. The secondary objectives include overall survival, and safety.Clinical trial identificationNCT06373380.Legal entity responsible for the studyWinston Wong, MD [Principal Investigator]. Memorial Sloan Kettering Cancer Center.FundingHookipa Pharma.DisclosureA.L. Ho: Financial Interests, Personal, Invited Speaker, discussed head and neck cancer therapies: Chinese American Hematologist and Oncologist Network; Financial Interests, Personal, Invited Speaker, Discussed salivary cancer therapies: Lurie Cancer Center (Northwestern); Financial Interests, Personal, Invited Speaker, discussed thyroid cancer therapies: Physician Education Resource; Financial Interests, Personal, Invited Speaker, Discussed thyroid cancer therapies: Endocrine Society; Financial Interests, Personal, Invited Speaker, Discussed head and neck cancer therapies: University of Pittsburgh Medical Center; Financial Interests, Personal, Invited Speaker, Discussed thyroid cancer therapeutics: New York University; Financial Interests, Personal, Advisory Board, Serve on DSMC: Affyimmune; Financial Interests, Personal, Other, Serve on the NCI Head and Neck Steering Committee: National Cancer Institute; Financial Interests, Personal, Advisory Board, Member of advisory board: Exelixis, Remix Therapeutics, Elevar Therapeutics, Prelude Therapeutics, Eisai, Ayala, Kura Oncology; Financial Interests, Personal, Other, Member of Safety Monitoring Committee: Kura Oncology; Financial Interests, Personal, Advisory Board, Member of advisory board: Merck; Financial Interests, Personal, Other, Consultant: ExpertConnect; Financial Interests, Personal, Advisory Board, Member of advisory board and consulting: Rgenta; Financial Interests, Personal, Advisory Board, Advisory Board: Coherus; Financial Interests, Personal, Advisory Board: Nested Therapeutics; Financial Interests, Personal, Full or part-time Employment: Memorial Sloan Kettering Cancer Center; Financial Interests, Institutional, Other, Listed as inventor for: Memorial Sloan Kettering Cancer Center; Financial Interests, Institutional, Coordinating PI, Serve as PI. also served on paid advisory board: Ayala; Financial Interests, Institutional, Coordinating PI, Serve as trial PI, also serve on paid SMC/advisory board: Kura Oncology; Financial Interests, Institutional, Local PI, Trial PI and served on an advisory board: Elevar Therapuetics; Financial Interests, Institutional, Coordinating PI, PI of IIT: Novartis, Merck, Bristol Meyer Squibb; Financial Interests, Institutional, Coordinating PI, PI of several IIT trials: Bayer; Financial Interests, Institutional, Coordinating PI, PI of trial: Bioatla, TILT Biotherapeutics, Genentech Roche, Astellas, Celldex; Financial Interests, Institutional, Local PI, PI of trial: OncC4; Financial Interests, Institutional, Coordinating PI, PI of several IITs: AstraZeneca; Financial Interests, Institutional, Coordinating PI, PI of trial and was part of paid advisory board: Eisai; Financial Interests, Institutional, Local PI, co-PI of trial: Poseida Therapuetics; Financial Interests, Institutional, Local PI: Hookipa; Financial Interests, Institutional, Coordinating PI, PI of IST clinical trial: Verastem; Financial Interests, Institutional, Coordinating PI, PI of Remix sponsored trial: Remix Therapeutics; Non-Financial Interests, Advisory Role: Cellestia, Inxmed; Non-Financial Interests, Member of Board of Directors: International Thyroid Oncology Group; Non-Financial Interests, Leadership Role: International Rare Cancer Initiative; Non-Financial Interests, Leadership Role, for the head and neck working group: Alliance for Clinical Trials in Oncology. N. Riaz: Financial Interests, Institutional, Research Funding: Pfizer, Repare Therapeutics, BMS. D. Pfister: Financial Interests, Institutional, Local PI: Akeso Biopharma, Hookipa Biotech. N. Lee: Financial Interests, Personal, Advisory Board: Merck, Merck Serono, Nanobioix, Galera, LEO SAB; Financial Interests, Personal, Stocks/Shares: LEO SAB; Financial Interests, Personal, Speaker, Consultant, Advisor: Shanghai Medical Technology Co, Ltd, Yingming Consulting, Varian. E.J. Sherman: Financial Interests, Personal, Advisory Board: Affyimmune, Eli Lilly, Eisai, Novartis; Financial Interests, Institutional, Coordinating PI: Fore Therapeutics. W. Wong: Financial Interests, Institutional, Principal Investigator: Hookipa, BioAtla. All other authors have declared no conflicts of interest.