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Proffered Paper - Sarcoma

5471 - ADP-A2M4 (MAGE-A4) in patients with Synovial Sarcoma

Date

30 Sep 2019

Session

Proffered Paper - Sarcoma

Topics

Clinical Research;  Immunotherapy;  Rare Cancers

Tumour Site

Soft Tissue Sarcomas

Presenters

Brian Van Tine

Citation

Annals of Oncology (2019) 30 (suppl_5): v683-v709. 10.1093/annonc/mdz283

Authors

B.A. Van Tine1, M.O. Butler2, D. Araujo3, M.L. Johnson4, J. Clarke5, D. Liebner6, K. Odunsi7, A.J. Olszanski8, S. Basu9, F. Brophy10, T. Holdich11, T. Trivedi10, R.G. Amado10, D.S. Hong12

Author affiliations

  • 1 Department Of Medical Oncology And Hematology, Washington University School of Medicine, 63110 - St. Louis/US
  • 2 Department Of Medical Oncology And Hematology, Princess Margaret Hospital, M5G 2M9 - Toronto/CA
  • 3 Sarcoma Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 4 Medical Oncology, Sarah Cannon Research Institute-Cancer Centre, 37203 - Nashville/US
  • 5 Department Of Medicine, Division Of Medical Oncology, Duke University School of Medicine, NC 27710 - Durham/US
  • 6 Internal Medicine, Ohio State University, 43210 - Columbus/US
  • 7 Gynecologic Oncology, Roswell Park Cancer Institute, 14263 - Buffalo/US
  • 8 Medical Oncology, Fox Chase Cancer Center, 19111-2497 - Philadelphia/US
  • 9 Translational Sciences, Adaptimmune, 19112 - Philadelphia/US
  • 10 Clinical Development, Adaptimmune, 19112 - Philadelphia/US
  • 11 Clinical Development, Adaptimmune Ltd, OX14 4RY - Abingdon/GB
  • 12 Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, 77030 - Houston/US

Resources

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Abstract 5471

Background

This study (NCT03132922) evaluates safety, tolerability, and antitumor activity of ADP-A2M4, genetically engineered autologous specific peptide enhanced affinity receptor (SPEAR) T-cells directed towards a MAGE-A4 peptide expressed in the context of HLA-A*02. Here, we report on a subset of patients (pts) with synovial sarcoma (SS).

Methods

In this first-in-human T-cell dose-escalation study, pts who are HLA-A*02+ (excluding *02:05, *02:07), have inoperable or metastatic MAGE-A4+ disease, and meet entry criteria are eligible for treatment. Following apheresis, T-cells are isolated, transduced with MAGE-A4c1032TCR, and expanded. The lymphodepletion chemotherapy increased in intensity as the study progressed, with max dose of 30 mg/m2/d fludarabine x 4 d and 1800 mg/m2/d cyclophosphamide x 2 d. During dose escalation, 3 pts with various tumor types received 0.1x109 (±20%), 1x109 (range: 0.5 – 1.2 × 109), or 5x109 (range: 1.2 – 6 × 109) transduced cells and were monitored for dose-limiting toxicities (DLTs). During expansion, 30 pts (not only SS) will be treated with 1.2 – 10 x 109 transduced cells. Disease is assessed per RECIST by CT/MRI at wk 6, 12, 18, and 24, and every 3 mo for 2 yr, then every 6 mo or until progression. Correlative studies will investigate transduced cell persistence, phenotype, and function, and serum and tumor microenvironment factors.

Results

No DLTs were reported. ADP-A2M4 was well tolerated, with adverse events consistent with chemotherapy or other immunotherapies. 10 pts with SS have been treated in cohort 3 and the expansion phase (30Apr19). Median T-cell dose was 9.7 x 109 (4.49 - 9.98 x 109). 8 pts have post-baseline tumor assessments. There are 3 confirmed partial responses (PR) (-86%, -44%, -54), and 1 unconfirmed PR (-31%) at wk 6. Best response was stable disease in 3 pts (-27% and -15%, ongoing, and +12%, progressed) and progressive disease in 1. 2 pts have yet to be assessed. Ex vivo analysis of transduced cells from peripheral blood and tumor showed cells were cytolytic and activated in an antigen-specific manner.

Conclusions

ADP-A2M4 induced clinical responses in pts with SS. Transduced T-cells expand upon exposure to antigen and are functional. Updated data from this ongoing study will be presented.

Clinical trial identification

NCT03132922, First posted on April 28, 2017.

Editorial acknowledgement

Debra Brocksmith, MB ChB, PhD, of Envision Pharma Group; contracted by Adaptimmune.

Legal entity responsible for the study

Adaptimmune.

Funding

Adaptimmune.

Disclosure

B.A. Van Tine: Research grant / Funding (self): Pfizer; Research grant / Funding (self): Tracon; Research grant / Funding (self): Merck; Advisory / Consultancy: Epizyme; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: CytRX; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: Immune Design; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Plexxicon; Advisory / Consultancy: Adaptimmune; Speaker Bureau / Expert testimony: Caris. M.O. Butler: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): Roche; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: GSK; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Immunovaccine; Research grant / Funding (institution): Takara Bio. M.L. Johnson: Research grant / Funding (institution): BerGenBio; Research grant / Funding (institution): Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Genmab; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Additional travel from: Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Bristol-Myers Squibb, Exelixis, Incyte, Merck, Sysmex Inostics, Vapotherm: Genentech; Research grant / Funding (institution): Stemcentrix; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Checkpoint Therapeutics; Research grant / Funding (institution): Array Biopharma; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Apexigen; Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie; Research grant / Funding (institution): Tarveda; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution), Additional advisory for: Gelgene, Boehringer Ingelheim, Sanofi, LOXO, Calithera, Merck, Araxes Pharma, Mersana Therapeutics, BeiGene, Incyte, Guardant Health, Bristol-Myers Squibb, Ribon Therapeutics: Syndax; Research grant / Funding (institution), Additional grant funding from: Boehringer Ingelheim, Sanofi, Hengrui Therapuetics INC, Merck, Daiichi-Sankyo, Lycera, G1 Therapeutics, Dynavax, LOXO, Cytomx, BeiGene, Birdie, Corvus, Incyte, Genocea, Gritstone, Amgen, Bristol-Myers Squibb, Kadmon, Clovis, Acerta, OncoMed, Guardant Health, Takeda, Shattuck Labs, GSK: Neovia. J. Clarke: Research grant / Funding (self): MedPacto; Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Genentech; Research grant / Funding (self): Spectrum; Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Bayer; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Moderna; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Guardant; Advisory / Consultancy: AstraZeneca. D. Liebner: Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy: Blueprint Medicines. K. Odunsi: Research grant / Funding (self): ITeos Therapeutics. A.J. Olszanski: Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Array; Advisory / Consultancy, Research grant / Funding (self): EMD Serono; Advisory / Consultancy: Iovance; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (self): Alkermes; Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Astellas; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Checkmate Pharmaceutics; Research grant / Funding (self): GSK; Research grant / Funding (self): Immunocore; Research grant / Funding (self): Intensity Therapeutics; Research grant / Funding (self): Kartos; Research grant / Funding (self): Kura; Research grant / Funding (self): Oncoceutics; Research grant / Funding (self): Targovax. S. Basu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. F. Brophy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. T. Holdich: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. T. Trivedi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. R.G. Amado: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Adaptimmune. D.S. Hong: Research grant / Funding (self): AbbVie; Advisory / Consultancy, Research grant / Funding (self): Adaptimmune; Research grant / Funding (self): Amgen; Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Bayer; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Daiichi-Sankyo; Research grant / Funding (self): Eisai; Research grant / Funding (self): Fate Therapeutics; Advisory / Consultancy, Research grant / Funding (self): Genentech; Research grant / Funding (self), Travel / Accommodation / Expenses: Genmab; Research grant / Funding (self): Ignyta; Advisory / Consultancy, Research grant / Funding (self): Infinity; Research grant / Funding (self): Kite; Research grant / Funding (self): Kyowa; Research grant / Funding (self): Lilly; Research grant / Funding (self), Travel / Accommodation / Expenses: LOXO; Research grant / Funding (self): MedImmune; Research grant / Funding (self): Merck; Research grant / Funding (self), Additional grant funding from: miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartics, Pfizer, Seattle Genetics, Takeda. Additional advisory consulting for: Alpha Insights, Axiom, Baxter, GLG, Group H, Guidepoint Global, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, Trieza Therapeutics, WebMD; Travel support from MiRNA, AACR, ASCO, SITC; ownership interests in Molecular Match, OncoResponse, Presagia Inc: Mirati. All other authors have declared no conflicts of interest.

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