961MO - Safety, efficacy, immunogenicity of arenavirus-based vectors HB-201 and HB-202 in patients with HPV16+ cancers

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 (1–10) 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 1.2–5.9 months. All 6 evaluable patients that received HB-201/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.

Editorial acknowledgement

Writing and editorial support was provided by Margaret Van Horn, PhD, of AlphaBioCom, LLC, and was funded by Hookipa Biotech GmbH.

Legal entity responsible for the study

Hookipa Biotech GmbH.

Funding

Hookipa Biotech GmbH.

Disclosure

M.R. Posner: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Advisory Role: BioNTech; Financial Interests, Advisory Role: Kura; Financial Interests, Advisory Board: Cel-Sci; Financial Interests, Advisory Board: Merck; Financial Interests, Advisory Role: Hookipa; Financial Interests; Advisory Role: Naveris; Financial Interests, Institutional, Funding: Formation Biologics; Financial Interests, Institutional, Funding: Innate; Financial Interests, Institutional, Funding: Hookipa Pharma; Financial Interests, Institutional, Funding: Sensei; Financial Interests, Institutional, Funding: Regeneron (Clinical Trials); Financial Interests, Royalties: Alopexx; Financial Interests, Institutional, Royalties: anti-Pseudomonas antibody; Financial Interests, Institutional, Royalties: anti-Staphylococcal monoclonal antibody; Financial Interests, Royalties: UpToDate editor; Financial Interests, Advisory Board: Hookipa Pharma. A.L. Ho: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Institutional, Other, Honoraria: Massachusetts General Hospital; Financial Interests, Institutional, Other, Honoraria: Winship Cancer Center/Emory; Financial Interests, Institutional, Other, Honoraria: Leidos/NIH; Financial Interests, Institutional, Other, Honoraria: ASTRO; Financial Interests, Institutional, Other, Honoraria: Rasopathy conference; Financial Interests, Advisory Role: Eisai; Financial Interests, Advisory Role: Sanofi Genzyme; Financial Interests, Advisory Role: Ayala Pharmaceuticals; Financial Interests, Advisory Role: Regeneron; Financial Interests, Advisory Role: CureVac; Financial Interests, Advisory Role: Klus Pharm; Financial Interests, Advisory Role: Prelude Therapeutics; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Kura Oncology; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: Bristol-Myers Squibb; Financial Interests, Advisory Role: Genentech/Roche; Financial Interests, Advisory Role: Sun Pharmaceuticals; Financial Interests, Advisory Role: TRM Oncology; Financial Interests, Advisory Role: McGivney Global Advisors; Financial Interests, Advisory Role: Rgenta; Financial Interests, Advisory Role: Exelixis; Financial Interests, Advisory Role: Affyimmune; Financial Interests, Advisory Role: Inxmed; Financial Interests, Speaker’s Bureau: Medscape; Financial Interests, Speaker’s Bureau: Novartis; Financial Interests, Speaker’s Bureau: Omniprex America; Financial Interests, Personal, Funding, For Clinical Trials: Allos Therapeutics; Financial Interests, Personal, Funding, For Clinical Trials: Astellas Pharma; Financial Interests, Personal, Funding, For Clinical Trials: AstraZeneca; Financial Interests, Personal, Funding, For Clinical Trials: Ayala Pharmaceuticals; Financial Interests, Personal, Funding, For Clinical Trials: Bayer; Financial Interests, Personal, Funding, For Clinical Trials: Bristol-Myers Squibb; Financial Interests, Personal, Funding, For Clinical Trials: Daiichi Sankyo; Financial Interests, Personal, Funding, For Clinical Trials: Eisai; Financial Interests, Personal, Funding, For Clinical Trials: Elevar Therapeutics; Financial Interests, Personal, Funding, For Clinical Trials: Genentech/Roche; Financial Interests, Personal, Funding, For Clinical Trials: Celldex; Financial Interests, Personal, Funding, For Clinical Trials: Kura Oncology; Financial Interests, Personal, Funding, For Clinical Trials: Lilly; Financial Interests, Personal, Funding, For Clinical Trials: Merck; Financial Interests, Personal, Funding, For Clinical Trials: Novartis; Financial Interests, Personal, Funding, For Clinical Trials: Pfizer; Financial Interests, Personal, Funding, For Clinical Trials: Kura Oncology; Financial Interests, Other, Travel/Accommodation/Expenses: Ayala Pharmaceuticals; Financial Interests, Other, Travel/Accommodation/Expenses: Ignyta; Financial Interests, Other, Travel/Accommodation/Expenses: Janssen Oncology; Financial Interests, Other, Travel/Accommodation/Expenses: Klus Pharma; Financial Interests, Other, Travel/Accommodation/Expenses: Kura Oncology; Financial Interests, Other, Travel/Accommodation/Expenses: Merck; Financial Interests, Other, Travel/Accommodation/Expenses: Shanghai Jia Tong University; Financial Interests, Stocks/Shares: Rgenta; Financial Interests, Member of the Board of Directors: International Thyroid Oncology Group. J. Niu: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Advisory Role: Boehringer Ingelheim; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Blueprint Medicines; Financial Interests, Advisory Role: Immvira; Financial Interests, Advisory Role: Johnson&Johnson; Financial Interests, Advisory Role: Takeda; Financial Interests, Advisory Role: Exelixis; Financial Interests, Advisory Role: Beigene; Financial Interests, Advisory Role: Mirati Therapeutics. L. Nabell: Other, Principal Investigator, NCT04180215: Hookipa Pharma. R.S. Leidner: Other, Principal Investigator, NCT04180215: Hookipa Pharma; Financial Interests, Advisory Role: Sanofi/Regeneron; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: Bristol-Myers Squibb; Financial Interests, Advisory Role: Oncolys Biopharma; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: MedImmune; Financial Interests, Other, Travel/Accommodation/Expenses: Sanofi/Regeneron; Financial Interests, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Other, Travel/Accommodation/Expenses: Merck; Financial Interests, Other, Travel/Accommodation/Expenses: Bristol-Myers Squibb. J. Nieva: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Bayer; Financial Interests, Advisory Role: Western Oncolytics; Financial Interests, Advisory Role: Fujirebio Diagnostics; Financial Interests, Advisory Role: Takeda; Financial Interests, Advisory Role: Roche/Genentech; Financial Interests, Advisory Role: Turnstone; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Stocks/Shares: Epic Sciences; Financial Interests, Stocks/Shares: Cansera; Financial Interests, Royalties: Patent Pending - movement and unexpected health care encounters. D.L. Richardson: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Genentech/Roche; Financial Interests, Advisory Role: Deciphera; Financial Interests, Advisory Role: Mersana; Financial Interests, Advisory Role: Tesaro/GlaxoSmithKline; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: Mersana; Financial Interests, Institutional, Funding: Tesaro/GlaxoSmithKline; Financial Interests, Institutional, Funding: Aravive; Financial Interests, Institutional, Funding: ArQule, Inc.; Financial Interests, Institutional, Funding: Decphera; Financial Interests, Institutional, Funding: Harpoon Therapeutics; Financial Interests, Institutional, Funding: Innovent Biologics; Financial Interests, Institutional, Funding: Karyopharm; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Syros Pharmaceuticals; Financial Interests, Institutional, Funding: Five Prime Therapeutics; Financial Interests, Institutional, Funding: Hookipa Biotech; Financial Interests, Institutional, Funding: FujiFilm; Financial Interests, Institutional, Funding: Shattuck Labs; Financial Interests, Institutional, Funding: Plexxikon. A.T. Pearson: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Advisory Role: Prelude Therapeutics; Financial Interests, Expert Testimony: Smith Haughey Rice & Roegge. D. Wang: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Advisory Role: Castle BioSciences; Financial Interests, Advisory Role: Qurgen; Financial Interests, Other, Travel/Accommodation/Expenses: Castle BioSciences; Financial Interests, Other, Travel/Accommodation/Expenses: Qurgen. K. Chung: Other, Principal Investigator: Hookipa Pharma. D.R. Adkins: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: Cue Biopharma; Financial Interests, Advisory Role: BLU; Financial Interests, Advisory Role: Exelixis; Financial Interests, Advisory Role: Kura; Financial Interests, Advisory Role: Twoxar; Financial Interests, Advisory Role: Vaccinex; Financial Interests, Advisory Role: Zilio; Financial Interests, Advisory Role: Targimmune; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Celgene/BMS; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Atara Bio; Financial Interests, Institutional, Funding: Blueprint Medicine; Financial Interests, Institutional, Funding: Celldex; Financial Interests, Institutional, Funding: Aduro; Financial Interests, Institutional, Funding: Enzychem; Financial Interests, Institutional, Funding: Kura; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Innate; Financial Interests, Institutional, Funding: Sensei; Financial Interests, Institutional, Funding: Matrix Biomed; Financial Interests, Institutional, Funding: ISA; Financial Interests, Institutional, Funding: Cofactor; Financial Interests, Institutional, Funding: Cue Biopharma; Financial Interests, Institutional, Funding: Debiopharm; Financial Interests, Institutional, Funding: Epizyme; Financial Interests, Institutional, Funding: Hookipa; Financial Interests, Institutional, Funding: Shanghai De Novo; Financial Interests, Institutional, Funding: Roche. A. Pimentel: Other, Principal Investigator: Hookipa Pharma; Other, Principal Investigator: Turnstone Biologics, Corp; Other, Principal Investigator: Ludwig Institute for Cancer Research, Ltd; Other, Principal Investigator: Isofol Medical AB; Other, Principal Investigator: Hoosier Cancer Research Network, Inc.; Other, Principal Investigator: ECOG-ACRIN; Financial Interests, Advisory Role: Taiho Oncology; Financial Interests, Advisory Role: QED Therapeutics; Financial Interests, Advisory Role: Bristol-Myers Squibb Company; Financial Interests, Stocks/Shares: Pfizer; Financial Interests, Stocks/Shares: BioNTech. S. Wong: Other, Principal Investigator: Hookipa Pharma. C. Iacobucci: Financial Interests, Stocks/Shares: BMS; Financial Interests, Stocks/Shares: Hookipa Pharma; Financial Interests, Full or part-time Employment: Hookipa Pharma. X. Qing: Financial Interests, Stocks/Shares: Hookipa Pharma; Financial Interests, Full or part-time Employment: Hookipa Pharma. K. Katchar: Financial Interests, Stocks/Shares: Hookipa Pharma; Financial Interests, Full or part-time Employment: Hookipa Pharma. K. Schlienger: Financial Interests, Other, Travel/Accommodation/Expenses: Hookipa Pharma; Financial Interests, Full or part-time Employment: Hookipa Pharma. I. Matushansky: Financial Interests, Stocks/Shares: Hookipa Pharma; Financial Interests, Full or part-time Employment: Hookipa Pharma; Financial Interests, Member of the Board of Directors: Crescendo Biologics; Financial Interests, Leadership Role: Hookipa Pharma. S. Fu: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Personal, Funding: Millenium Pharmaceuticals, Inc.; Financial Interests, Personal, Funding: Sorcimed Biopharma, Inc.; Financial Interests, Personal, Funding: Exelixis; Financial Interests, Personal, Funding: BeiGene; Financial Interests, Personal, Funding: Novocure; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Abbisko; Financial Interests, Institutional, Funding: Anaeropharma Science; Financial Interests, Institutional, Funding: Arrien Pharmaceuticals; Financial Interests, Institutional, Funding: BeiGene; Financial Interests, Institutional, Funding: BioAtla, LLC; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Eli Lilly & Co.; Financial Interests, Institutional, Funding: Hookipa Biotech; Financial Interests, Institutional, Funding: Huya Bioscience International; Financial Interests, Institutional, Funding: IMV, Inc; Financial Interests, Institutional, Funding: Innovent Biologics, Col., Ltd; Financial Interests, Institutional, Funding: Lyvgen Pharma; Financial Interests, Institutional, Funding: MacroGenics; Financial Interests, Institutional, Funding: Medivir AB; Financial Interests, Institutional, Funding: Millennium Pharmaceuticals, Inc.; Financial Interests, Institutional, Funding: Nerviano Medical Sciences; Financial Interests, Institutional, Funding: Neupharma, Inc; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Novocure; Financial Interests, Institutional, Funding: OncoMed Pharmaceuticals; Financial Interests, Institutional, Funding: Parexel International, LLC; Financial Interests, Institutional, Funding: Sellas Life Sciences Group; Financial Interests, Institutional, Funding: Sorcimed Biopharma, Inc.; Financial Interests, Institutional, Funding: Tolero Pharmaceuticals; Financial Interests, Institutional, Funding: National Institutes of Health/National Cancer Institute; Financial Interests, Institutional, Research Grant, P30CA016672 – Core Grant (CCSG Shared Resources): National Cancer Institute/National Institutes of Health; Financial Interests, Full or part-time Employment: MD Anderson - FT. D.G. Pfister: Other, Principal Investigator: Hookipa Pharma; Financial Interests, Advisory Role: Boehringer Ingelheim; Financial Interests, Advisory Role: Celgene; Financial Interests, Advisory Role: Bristol-Myers Squibb; Financial Interests, Advisory Role: Incyte; Financial Interests, Personal, Funding: Boehringer Ingelheim; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Funding: MedImmune; Financial Interests, Personal, Funding: Merck; Financial Interests, Personal, Funding: Regeneron; Financial Interests, Personal, Funding: Atara Biotherapeutics; Financial Interests, Personal, Funding: Kura; Financial Interests, Personal, Funding: Esai; Financial Interests, Personal, Funding: Ayala; Financial Interests, Personal, Funding: Plexxikon.