735MO - Updated safety and efficacy from SURPASS, the phase I trial of ADP-A2M4CD8, a next-generation autologous T-cell receptor T-cell therapy, in previously treated patients with unresectable or metastatic tumors

Background

ADP-A2M4CD8 is a next-generation, specific peptide enhanced affinity receptor T-cell therapy modified with addition of a CD8α co-receptor to treat human leukocyte antigen A*02–eligible patients (pts) with unresectable or metastatic tumors positive for the cancer testis antigen melanoma-associated antigen A4 (MAGE-A4). ADP-A2M4CD8 has demonstrated promising anti-tumor activity with a favorable benefit to risk profile in the ongoing phase 1 SURPASS trial.¹ Here we report updated clinical outcomes with additional pts treated.

Methods

The first-in-human trial consists of a modified 3+3 dose-escalation design with an expansion cohort. T-cells are obtained by leukapheresis, transduced with a lentiviral vector carrying the T-cell receptor and CD8α co-receptor genes, expanded in vitro, and infused back to the pt as ADP-A2M4CD8 following lymphodepleting chemotherapy. Safety, efficacy, pharmacokinetics, pharmacodynamics, and tumor biopsy characterization are evaluated.

Results

As of December 6, 2021, 29 pts (14 male, 15 female; all White) with a median age of 60 years (range: 31–75) received ADP-A2M4CD8 (1.02–9.95x10⁹ transduced T-cells). Median MAGE-A4 expression H-score was 260 (range: 130–300). Overall response rate per RECIST v1.1 by investigator review for all cancer types was 31%; disease control rate was 75.9%. Adverse events were consistent with those typically associated with nonmyeloablative lymphodepletion, cellular therapy, and/or disease. This trial is ongoing; data from additional pts treated by August 2022 will be presented.

Conclusions

ADP-A2M4CD8 continues to show a favorable benefit to risk profile in multiple MAGE-A4+ unresectable or metastatic tumors. An additional treatment cohort has been included in the updated trial protocol to understand the potential benefits of ADP-A2M4CD8 combined with nivolumab. Emerging data signals encouraging clinical outcomes, especially for gastroesophageal and ovarian cancers for which two phase 2 trials have been or will be initiated. ¹Hong DS, et al. E-poster 540P: ESMO 2021; Virtual.

Clinical trial identification

NCT04044859.

Editorial acknowledgement

This study was sponsored by Adaptimmune (Philadelphia, PA, USA). Writing and editorial support was from Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Adaptimmune.

Legal entity responsible for the study

Adaptimmune.

Funding

Adaptimmune.

Disclosure

D.S. Hong: Financial Interests, Institutional, Research Grant: AbbVie, Adaptimmune, Adlai-Nortye, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Deciphera, Eisai, Endeavor, Erasca, F. Hoffmann-La Roche, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa Kirin, Lilly, LOXO, Merck, Medimmune, Mirati, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, SeaGen, Takeda, TCR2, Teckro, Turning Point Therapeutics, Verstatem, VM Oncology; Financial Interests, Personal, Other, Travel accommodations, expenses: Bayer, Genmab, AACR, ASCO, SITC, Telperian; Financial Interests, Personal, Advisory Role: Adaptimmune, Alpha Insights, Acuta, Alkermes, Amgen, Aumbiosciences, Axiom, Baxter, Bayer, Boxer Capital, BridgeBio, COR2ed, COG, Ecor1, Genentech, Gilead, GLG, Group H, Guidepoint, HCW Precision, Immunogen, Infinity, Janssen, Liberium, Medscape, Numab, Oncologia Brasil, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, Seattle Genetics, ST Cube, Takeda, Tavistock, Trieza Therapeutics, Turning Point, WebMD, Ziopharm; Financial Interests, Personal, Ownership Interest: Molecular Match, OncoResponse, Telperian. E. Calvo: Financial Interests, Personal, Full or part-time Employment: START, HM Hospitales Group; Financial Interests, Personal, Leadership Role: START; Financial Interests, Personal, Stocks/Shares: START, Oncoart Associated; Financial Interests, Personal, Honoraria: HM Hospitales Group; Financial Interests, Personal, Advisory Role: Nanobiotix, Janssen-Cilag, PsiOxus Therapeutics, Seattle Genetics, Roche/Genentech, Amcure, TargImmune Therapeutics, Servier, Bristol Myers Squibb, PharmaMar, Alkermes, Amunix, Adcendo, Anaveon, AstraZeneca/MedImmune, BeiGene, Chugai Pharma, MonTa, MedSIR, MSD Oncology, Nouscom, Novartis, OncoDNA, Sanofi, Syneos Health, T-Knife, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: BeiGene, START; Financial Interests, Institutional, Research Grant: Achilles; Financial Interests, Personal, President and Founder: Foundation INTHEOS (Investigational Therapeutics in Oncological Sciences). J. Zugazagoitia: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Roche, Pfizer, Novartis, Guardant Health; Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Roche, AstraZeneca, NanString, Guardant Health; Financial Interests, Personal, Travel Honoraria: BMS, Pfizer, Roche, AstraZeneca, NanoString; Financial Interests, Personal, Research Grant: BMS, AstraZeneca, Roche. J. Charlson: Financial Interests, Institutional, Advisory Board: Adaptimmune; Financial Interests, Institutional, Advisory Role: Deciphera. M.O. Butler: Financial Interests, Institutional, Research Grant: Merck, Takara Bio; Financial Interests, Personal, Advisory Role: Merck, BMS, Novartis, Immunocore, Adaptimmune, EMD Serono, GSK, Sanofi, Instil Bio, Iovance, Pfizer; Financial Interests, Personal, Invited Speaker: Merck, BMS, Novartis, Pfizer; Financial Interests, Personal, Safety Review Committee: Adaptimmune, GSK. V. Moreno Garcia: Financial Interests, Personal, Advisory Role: Roche, Bayer, BMS, Janssen, Basilea; Financial Interests, Institutional, Principal Investigator: AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca, Bayer, Beigene, BioInvent International AB, BMS, Boehringer, Boheringer, Boston, Celgene, Daichii Sankyo, DEBIOPHARM, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Sponsor, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith. A. Cervantes: Financial Interests, Institutional, Research Grant: Genentech, Merck Serono, Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Adaptimmune, BeiGene, Bayer, Servier, Lilly, Novartis, Takeda, Astellas, Takeda, FibroGen; Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, Roche, Bayer, Servier, Pierre Fabre. B.A. Van Tine: Financial Interests, Personal, Advisory Role: Epizyme, CytRx, Janssen, Plexxicon, Bayer; Financial Interests, Personal, Consultant, Advisory Role/Speaker, Research/Trial Support, Travel Support: Lilly; Financial Interests, Personal, Speaker’s Bureau: Caris; Financial Interests, Personal, Research Grant, consulting/ad board: Pfizer; Financial Interests, Personal, Research Grant: Merck, Tracon; Financial Interests, Personal, Advisory Board: Immune Design, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Adaptimmune; Financial Interests, Institutional, Research Grant: Lilly, Merck; Financial Interests, Institutional, Trial Support: Oncothyreon, Gliknik, Celidex Therapeutics, ImClone Systems, Peregrine Pharmaceuticals, BIND Therapeutics, Regeneron Pharmaceuticals, MabVax Therapeutics, Millenium, AbbVie, Janssen Research Foundation, Jounce Therapeutics, EMD Serono, Puma Biotechnology, VentiRx Pharmaceuticals, Taiho Pharmaceuticals, Gilead Sciences, Incyte, Daiichi Pharmaceutical, Novartis, Pfizer, Acerta, Inventiv Health, Celgene, Sanofi, AstraZeneca, Merrimack Pharmaceuticals, Biothera Pharmaceuticals, Medimmune, Blueprint Medicines, Bristol Myers Squibb, Enzychem Lifesciences Corporation, Eisai, Genentech, Corvus, Johnson & Johnson, Threshold Pharmaceuticals, Bayer, BeiGene, GlaxoSmithKline, Molecular Insight Pharmaceuticals, Gem Pharmaceuticals, Deciphera Pharmaceuticals, Forma Therapeutics, Bavarian Nordic, Hoffmann-LaRoche, Caris Life Sciences, Morphotek, Soligenix, Eleison Pharmaceuticals, AADi, Immune Design, TRACON Pharmaceuticals, NanoCarrier, Advenchen Laboratories, Karyopharm Therapeutics, Hutchison MediPharma. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Apexigen, Array BioPharma, AstraZeneca, Atreca, BeiGene, Boehringer Ingelheim, Checkpoint Therapeutics, Corvus Pharmaceuticals, CytomX, Daiichi Sankyo, Dynavax, Lilly, EMD Serono, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Hengrui Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Merck, Mirati Therapeutics, Neovia Oncology, Novartis, OncoMed Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals, Sanofi, Seven and Eight Biopharmaceuticals, Shattuck Labs, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, University of Michigan, WindMIL, TCR2 Therapeutics, Arcus Biosciences, Ribon Therapeutics, Amgen; Financial Interests, Personal, Advisory Role, spouse: Astellas, Otsuka Pharmaceuticals; Financial Interests, Personal, Advisory Board: AbbVie, Achilles Therapeutics, AstraZeneca, Atreca, Boehringer Ingelheim, Calithera Biosciences, Genentech, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Incyte, Janssen, Lilly, Loxo Oncology, Merck, Mirati Therapeutics, Novartis, Pfizer, Ribon Therapeutics, Sanofi; Financial Interests, Personal, Advisory Role: Association of Community Cancer Center; Financial Interests, Personal and Institutional, food/beverage/travel expenses: AbbVie, Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, EMD Serono, Bristol Myers Squibb, Exelixis, Genentech/Roche, Incyte, Merck, Pfizer, Sysmex Inostics, Vapotherm, Janssen, Lilly, Novartis, Sanofi. Q. Lin: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. T. Annareddy: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. F. Brophy: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. R. Broad: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. A. Derrac Soria: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. J. Navenot: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. J. Saro: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. E. Norry: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. J.M. Clarke: Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb, Genentech, Spectrum, Adaptimmune, Medpacto, Bayer, AbbVie, Moderna, GlaxoSmithKline, Array, AstraZeneca, Grid Therapeutics, CBMG; Financial Interests, Personal, Invited Speaker: Merck, AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, Pfizer, NGM Biopharmaceuticals, Spectrum, Genentech, Novartis, Turning Point, G1 Therapeutics, Vivacitas. All other authors have declared no conflicts of interest.