1019O - Clinical and translational data from the phase I SURPASS trial of ADP-A2M4CD8 T cell receptor (TCR) T cell therapy alone or combined with nivolumab in solid tumors

Background

ADP-A2M4CD8 is a TCR T-cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), modified with a CD8α coreceptor, to treat human leukocyte antigen A*02–eligible patients (pts) with unresectable/metastatic solid tumors. ADP-A2M4CD8 monotherapy has demonstrated an acceptable benefit-to-risk profile and encouraging anti-tumor activity in the ongoing phase 1 SURPASS trial. Nevertheless, inhibition of immunosuppressive pathways may improve anti-tumor responses; therefore, new SURPASS cohorts include ADP-A2M4CD8 combined with nivolumab or pembrolizumab. We report data from pts receiving monotherapy and nivolumab combination therapy.

Methods

T-cells are obtained by leukapheresis, transduced with a lentiviral vector carrying the TCR and CD8α coreceptor genes, expanded ex vivo, and infused back to the pt following lymphodepleting chemotherapy. ∼Four weeks after ADP-A2M4CD8 infusion, a subset of pts also received nivolumab 480 mg every 4 weeks until unacceptable toxicity/disease progression. Primary and secondary objectives are safety and anti-tumor activity, respectively.

Results

As of March 9, 2023, 51 pts with a median age of 60 years (range: 31–75) mainly with melanoma, non-small cell lung, ovarian, gastroesophageal, head and neck, or urothelial cancers received 1.02–9.95x10⁹ ADP-A2M4CD8 T-cells. Median (range) number of prior lines of therapy was 3 (1–8) and MAGE-A4 expression H-score was 250 (90–300). The four most common adverse events related to T-cell therapy were cytokine release syndrome (n=38 [74.5%]; 7 [13.7%] were Grade≥3), neutropenia (27.5%), pyrexia and fatigue (each 21.6%). Overall response rate per RECIST v1.1 by investigator review in monotherapy pts (n=45) was 35.6% (2 complete response, 14 partial response [PR]). Median duration of response was 20.79 weeks (95%CI: 11.6, 30.9). In pts assigned to nivolumab combination (n=6), there was 1 PR, 3 stable disease, and 2 not evaluable (2 pts have not received nivolumab and have no post-baseline RECIST assessment). Data from additional pts treated by August 2023 will be presented.

Conclusions

ADP-A2M4CD8 continues to show an acceptable benefit-to-risk profile, including in pts receiving nivolumab combination therapy.

Clinical trial identification

NCT04044859.

Editorial acknowledgement

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

Legal entity responsible for the study

Adaptimmune.

Funding

Adaptimmune.

Disclosure

V. Moreno Garcia: Financial Interests, Personal, Advisory Board: AstraZeneca, Basilea, Bayer, BMS, Janssen, Roche, START; Financial Interests, Institutional, Principal Investigator: Abbvie, AceaBio, Adaptimmune, ADC therapeutics, Aduero, Agenus, Amcure, Amgen, Astellas, AstraZeneca, Bayer, Beigene, BioInvent International AB, BMS, Boehringer, Celgene, Daiichi 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, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith. E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Chugai, Diaccurate, Elevation Oncology, Ellipses Pharmacy, Genmab, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Seriver, SyneosHealth, T-knife, TargImmune; Financial Interests, Personal, Invited Speaker: OncoDNA; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Member of Board of Directors, External Independent member of Board of Directors: PharmaMar; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Ownership Interest: Oncoart Associated, START; Financial Interests, Personal, Steering Committee Member, Member of Data Monitoring Committee: BieGene, Merus, Sanofi; Financial Interests, Personal, Steering Committee Member: Novartis; Financial Interests, Personal, Advisory Role, Non-for-profit foundation: CRIS Cancer Foundation, non-for-profit “CRIS contra el cáncer” Foundation; Financial Interests, Personal, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Financial Interests, Personal, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) non-for-profit Foundation; Financial Interests, Personal, Member of Board of Directors, Non-for-profit Foundation, trustee: Non-for-profit Foundation PharmaMar. A. Asch: Financial Interests, Personal, Other, Education: Gilead Sciences, Inc., Acrotech Biopharma LLC. M.O. Butler: Financial Interests, Personal, Speaker’s Bureau: BMS, Merck, Novartis, Sanofi, Pfizer; Financial Interests, Personal, Advisory Board: Merck, BMS, Novartis, Adaptimmune, Instil Bio, Iovance, Sun Pharma, GSK, Sanofi, LaRoche Possey, Pfizer, Medison, IDEAYA, Regeneron; Financial Interests, Personal, Research Grant: Merck, Takara Bio; Financial Interests, Personal, Research Grant, Quality improvement support from Novartis: Novartis. J. Zugazagoitia: Financial Interests, Personal, Speaker’s Bureau: MSD, BMS, Sanofi, AstraZeneca, Roche, NanoString; Financial Interests, Personal, Advisory Board: Sanofi, BMS, Novartis; Financial Interests, Personal, Research Grant: Astrazenece, Roche, BMS. J. Charlson: Financial Interests, Personal, Other, Paid instructor: Deciphera; Financial Interests, Personal, Other, Consultant: Deciphera. A. Cervantes: Financial Interests, Institutional, Advisory Board: Abbvie, Amgen, AnHeart Therapeutics, GSK, Merck Serono, Roche, Transgene; Financial Interests, Institutional, Invited Speaker: Amgen, Foundation Medicine, Merck Serono, Roche; Financial Interests, Personal, Other, Associate editor: Annals of Oncology, ESMO Open; Financial Interests, Personal, Other, Editore in Chief: Cancer Treatment Reviews; Financial Interests, Institutional, Research Grant, Principal investigator: Actuate Therapeutic, Astellas Pharma; Financial Interests, Institutional, Research Grant, Principal investigato: Adaptimmune, Affimed, Amcure, Amgen, Astrzeneca, Bayer, Beigene, BMS, F. STAR Therapeutics, FibroGen, Genentech, Gilead, Janssen, Lilly, MedImmune, Merck Serono, MSD, Natera, Novartis, Ribon Therapeutics, Roche, Seamless, Servier, Sierra, Takeda; Non-Financial Interests, Institutional, Other, Scientific Director: INCLIVA Biomedical Research Institute,. 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Clarke: Financial Interests, Personal, Other, Consultant: Novartis Turning Point, G1 Therapeutics Vivacitas, Omega, Amgen, Corbus, Sanofi; Financial Interests, Personal, Research Grant: Bristol-Myers Squibb, Genentech, Spectrum, Adaptimmune, Medpacto, Bayer, AbbVie, Moderna, GSK, Array, AstraZeneca, Grid Therapeutics, CBMG; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. M.L. Johnson: Financial Interests, Institutional, Research Funding, Paid to institution: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAlta, Black Diamond, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Convus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lily, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate THerapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals / Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, Universoty of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics; Financial Interests, Institutional, Advisory Board, Paid to Institution: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology; Financial Interests, Institutional, : Black Diamond. M. Wileman, A. Liddle, R. Naidoo, F. Brophy, M. Rosenberg: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. D. Jolliffe: Financial Interests, Personal, Stocks/Shares: Adaptimmune; Financial Interests, Personal, Full or part-time Employment: Adaptimmune. D. Williams: Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. E. Norry: Financial Interests, Personal, Officer: Adaptimmune; Financial Interests, Personal, Full or part-time Employment: Adaptimmune; Financial Interests, Personal, Stocks/Shares: Adaptimmune. D.S. Hong: Financial Interests, Personal, Other, Consulting: Gilead Sciences, Inc., Bayer, Pfizer, Abbvie; Financial Interests, Personal, Other, Education: Gilead.