921P - HB-200 arenavirus-based immunotherapy plus pembrolizumab as a first-line treatment of patients with recurrent/metastatic HPV16 positive head and neck cancer

Background

Treatment options are limited for patients with recurrent/metastatic (R/M) human papillomavirus (HPV) 16+ head and neck squamous cell carcinoma (HNSCC). HB-200 is comprised of an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively. HB-200 vectors express the same non-oncogenic HPV16 E7E6 fusion protein and induce E6 and E7-specific CD8 T cell responses. Previously, we reported the recommended phase 2 dose (RP2D) and antitumor activity of HB-200 monotherapy. Here, we report preliminary phase 2 results of HB-200 therapy in combination with pembrolizumab as first-line (1L) treatment of patients with HPV16+ programmed death ligand 1 (PD-L1)+ R/M HNSCC.

Methods

A run-in with HB-201 1-vector plus pembrolizumab was conducted prior to initiation of HB-200 plus pembrolizumab. HB-200 was administered intravenously (every 3 weeks [Q3W] then Q6W) in combination with pembrolizumab (200 mg Q3W or 400 mg Q6W, as indicated). Two dose levels of HB-200 were explored. Safety, immunogenicity and preliminary antitumor activity were assessed.

Results

As of March 31, 2023, 20 patients with checkpoint inhibitor-naïve, HPV16+ PD-L1+ R/M HNSCC (19 oropharynx) were treated with HB-200 plus pembrolizumab in the 1L setting. Characteristics of this cohort included: median age 66 years (range 50-76), 19 (95%) male, 17 (84%) White, 7 (35%) with ≥ 10 pack/year smoking history, and 10 (50%) tumors with PD-L1 combined positive score ≥ 20. Treatment-related adverse events (AEs) included: Grade ≥3 AEs in 2 (10%) patients and serious AEs in 1 (5%). No treatment-related discontinuations or deaths were reported. Among 14 evaluable patients (those with ≥ 2 tumor response assessments) receiving HB-200 plus pembrolizumab, the overall response rate was 43% (1 complete, 5 partial, all confirmed) and the disease control rate was 71%.

Conclusions

Preliminary data with HB-200 arenavirus-based immunotherapy plus pembrolizumab demonstrate a favorable safety profile and preliminary efficacy when given as a 1L treatment of patients with R/M HPV16+ PD-L1+ HNSCC. Clinical trial# NCT04180215.

Clinical trial identification

H-200-001 August 01, 2019.

Editorial acknowledgement

Legal entity responsible for the study

Hookipa Biotech GmbH.

Funding

HOOKIPA Pharma Inc.

Disclosure

L. Nabell: Non-Financial Interests, Personal and Institutional, Member: NCCN; Financial Interests, Institutional, Local PI: Hookipa Pharma Inc. A.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, Full or part-time Employment: Memorial Sloan Kettering Cancer Center; Financial Interests, Personal, Stocks/Shares, options: Rgenta Therapeutics; 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; 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. M.R. Posner: Financial Interests, Personal, Advisory Board, Attended an advisory board in 2023: Merus; Financial Interests, Personal, Other, Chairman external DSMC for multiple randomized head and neck trials, ongoing and active: Merck; Financial Interests, Personal, Other, Member external DSMC for Phase 1 study, ongoing: Caliditas; Financial Interests, Personal, Other, Consultant 2021-22, relationship not acive 2023: Cel Sci; Financial Interests, Personal, Other, Editor, Head and Neck Section, Royalties 2023: Uptodate/Thompson Reuters; Financial Interests, Personal, Royalties, Licensing feels for Patents for Human Moncclonal Antibodies issued to BIDMC and Licensed by BIDMC to outside companies 2023: Beth Israel Deaconess Medical Center; Financial Interests, Institutional, Local PI, Local PI Phase 3 study: ISA; Financial Interests, Institutional, Local PI, Local PI Phase 1 study: Hookipa; Financial Interests, Institutional, Other, Co-Investigator Phase 1 trial: Regeneron; Non-Financial Interests, Advisory Role, SAB member uncompensated: Frizent; Non-Financial Interests, Advisory Role, SAB Member, uncompensated: Vivan Therapeutics; Other, Other, Work closely with company to assess cliinical use and characteristics of HPV biomarker no compensation, share our clinical data with collaborators including company investigators and other clinical investigators in academic institutions: Naveris. P. Neupane: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck. A. Naqash: Financial Interests, Personal, Other, Social Media Editor and Consultant: JCO Precision Oncology; Financial Interests, Institutional, Local PI: Loxo, Surface Oncology, ADC Therapeutics, IGM Biosciences, Nikang Therapeutics, Inspirna, Revolution Medicine, Jacobio, Pionyr, Jazz, NGM; Financial Interests, Institutional, Coordinating PI: EMD Serono, Aravive; Non-Financial Interests, Other, Social Media Consultant and Scientific Committee Member: ASCO; Non-Financial Interests, Other, Educational Activity: OncLive; Non-Financial Interests, Leadership Role, Scientific Committee Co Chair: ORIEN; Non-Financial Interests, Leadership Role, Early Career Scientist Committee: SITC. S. Wong: Non-Financial Interests, Institutional, Non remunerated activity: Serano, Merck, GSK; Non-Financial Interests, Personal, Member of Board of Directors: RTOG Foundation Board; Non-Financial Interests, Personal, Leadership Role: NRG Oncology Head neck committee; Financial Interests, Institutional, Local PI: Hookipa Pharma Inc. J.J. Niu: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Daiichi Sankyo, Johnson & Johnson, BeiGene, Takeda, Mirati Therapeutics, Immvira, Bristol Myers Squibb, G1 Therapeutics; Financial Interests, Personal, Invited Speaker: Onclive, Naveris, Projects in Knowledge, Research to Practice, Optum Health Education. A.T. Pearson: Financial Interests, Personal, Advisory Board: Prelude Therapeutics, Elevar, AbbVie, Privo; Financial Interests, Institutional, Research Grant: AbbVie, Kura; Non-Financial Interests, Principal Investigator, Grant: Adenoid Cystic Carcinoma Research Foundation, Cancer Research Foundation. D.R. Adkins: Financial Interests, Personal, Advisory Role: Merck, Cue Biopharma, Blueprint Medicine, Exelixis, Immunitas, Kura Oncology, Targimmune Therapeutics, TwoXAR, Vaccinex, Xilio Therapeutics, Boehringer Ingelheim, Eisai Europe, Coherus Biosciences, Gilead Sciences, Jazz Pharmaceuticals; Financial Interests, Institutional, Local PI: Hookipa, Pfizer, Eli Lilly, Merck, Celgene/BMS, Novartis, AstraZeneca, Blueprint Medicine, Kura Oncology, CUE Biopharma, Cofactor Genomics, Debiopharm, ISA Pharmaceuticals, Gilead Sciences, BeiGene, Roche, Vaccinex, Adlai Nortye, BioAtla, Calliditas, Epizyme, Natco, Immutep, Tizona, Vaccinex, Genmab, Boehringer Ingelheim. A. Pimentel: Financial Interests, Institutional, Local PI: Bexion Pharmaceuticals, Gritstone bio, Pfizer, Bristol Myers Squibb, Turnstone Biologics, Hookipa Biotech, Isofol Medical AB, Hoosier Cancer Research Network. A.J. Rosenberg: Financial Interests, Personal, Advisory Role: Astellas, Novartis, EMD-Serono, Nanobiotix, Vaccitech, Eisai, Privo, Galectin, Coherus. D.L. Richardson: Financial Interests, Personal, Speaker, Consultant, Advisor: Mersana, AstraZeneca, Immunogen, GSK/Tesaro, Bayer, Foundation Medicine; Financial Interests, Institutional, Research Funding: GSK/Kline, Lilly, Celsion, Mersana, Hookipa, Syros, AstraZeneca, Shattuck Labs, Genentech/Roche, Innovent, Merck, Fujifilm, Plexxikon, Arch Oncology, Harpoon, Agenus; Non-Financial Interests, Personal, Member of Board of Directors: Society of Gynecologic Oncology; Financial Interests, Personal, Member of Board of Directors: National Ovarian Cancer Coaliation. T.A. Kaufmann: Financial Interests, Personal, Full or part-time Employment: Hookipa Pharma Inc. K. Katchar: Financial Interests, Personal, Full or part-time Employment: Hookipa Pharma Inc; Financial Interests, Personal, Stocks/Shares: Hookipa Pharma Inc. X. Qing: Financial Interests, Personal, Full or part-time Employment: Hookipa Pharma Inc; Financial Interests, Personal, Stocks/Shares: Hookipa Pharma Inc. C. Iacobucci: Financial Interests, Personal, Full or part-time Employment: Hookipa Pharma Inc; Financial Interests, Personal, Stocks/Shares: Innate pharma, Neogenomics, BMS. K. Schlienger: Financial Interests, Institutional, Officer: Hookipa Pharma; Financial Interests, Institutional, Stocks/Shares: Hookipa Pharma; Non-Financial Interests, Officer, Travel: Hookipa Pharma. D. Pfister: Financial Interests, Personal, Full or part-time Employment: Memorial Sloan Kettering Cancer Center; Financial Interests, Institutional, Local PI, PI of trial: Hookipa Biotech GmbH, Akeso Biopharma. All other authors have declared no conflicts of interest.