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Poster discussion session - Immunotherapy of cancer 1

6083 - Safety and Anti-Tumor Effects of MAGE-A10c796 TCR T-cells in Two Clinical Trials

Date

20 Oct 2018

Session

Poster discussion session - Immunotherapy of cancer 1

Topics

Clinical Research;  Immunotherapy;  Translational Research

Tumour Site

Presenters

Vincent Lam

Authors

V.K. Lam1, D.S. Hong2, J.V. Heymach3, G. Blumenschein3, M.O. Butler4, M. Johnson5, B. Creelan6, J.F. Gainor7, R. Govindan8, R. Mudad9, J. Neal10, F. Brophy11, F. Fang12, N. Hyland11, T. Holdich13, T. Trivedi11, E. Norry11, R.G. Amado12

Author affiliations

  • 1 Thoracic Head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030 - houston/US
  • 2 Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 77035 - Houston/US
  • 3 Thoracic Head And Neck Medical Oncology, MD ANDERSON CANCER CENTER, 77030 - HOUSTON/US
  • 4 Medical Oncology, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 5 Oncology, Sarah Cannon Research Institute, Tennessee Oncology, Nashville/US
  • 6 Medical Oncology, H. Lee Moffitt Cancer Center University of South Florida, 33612 - Tampa/US
  • 7 Hematology/oncology, Massachusetts General Hospital, 02114 - Boston/US
  • 8 Internal Medicine, Division Of Oncology, Washington University in St. Louis, St. Louis/US
  • 9 -, University of Miami, Miami/US
  • 10 -, Stanford University Medical Center, Stanford/US
  • 11 Clinical, Adaptimmune, 19112 - Philadelphia/US
  • 12 Clinical, Adaptimmune, 19103 - Philadelphia/US
  • 13 Medical Affairs, Adaptimmune Ltd, Abingdon/GB
More

Resources

Abstract 6083

Background

MAGE-A10 is expressed in ~10–50% of urothelial, melanoma, head & neck, and non-small cell lung (NSCLC) cancers. Affinity-enhanced autologous MAGE-A10c796T-cells directed toward MAGE-A10 in the context of HLA*02 (specific peptide enhanced affinity receptor [SPEAR] T-cells) are being tested in 2 clinical trials (NCT02592577; NCT02989064).

Methods

These first-in-human dose-escalation studies use a modified 3+3 design to evaluate safety. Patients (pts) are enrolled after receiving ≥1 line of therapy. Different cyclophosphamide/fludarabine lymphodepleting regimens are utilized based on dose group: group 1 target dose is 0.1 × 109 transduced cells, group 2 is 1 × 109, and group 3 is 5 × 109. Cohort expansion will occur at the maximum tolerated dose. Dose-limiting toxicities (DLTs) are adjudicated by a Safety Review Committee (SRC).

Results

As of 25 Jun 2018, 11 pts (7 male, median age 61 y) have been treated; 8 pts in group 1, 3 pts in group 2. AEs ≥ Grade 3 occurred in 9 pts; most frequently reported were lymphopenia (6), thrombocytopenia (5), anaemia (4), neutropenia (4), leukopenia (4), and hyponatremia (3). 7 pts reported serious AEs including: 2 CRS* (*=related to T-cell therapy), 2 dyspnoea and 1 each of abdominal pain, disease progression, haemoptysis*, neutropenia, pneumonia, respiratory failure, sepsis and thrombocytopenia. One Grade 4 CRS in group 1, which resolved with tocilizumab and steroids, was considered a DLT. For the 8 pts in group 1, their disease progressed. In Group 2, 1 pt died of pneumonia (MRSA, unrelated to T-cell therapy). 1 pt had stable disease (SD) at wk 4 but then progressed at wk 8; 1 pt had SD at wk 8 but progressed at wk 12. Cytokine levels were within ranges observed in other SPEAR T-cell studies. SPEAR T-cells were detectable in peripheral blood in both groups. After evaluating NSCLC group 2 data, the SRC agreed that both trials should dose escalate.

Conclusions

MAGE-A10 SPEAR T-cells at doses of 0.1 × 109 and 1 × 109 cells show no evidence of toxicity related to off-target binding or alloreactivity. Most AEs were consistent with those experienced by cancer patients undergoing chemotherapy or other immunotherapies. Enrolment in dose Group 3 (5 × 109 cells and increased conditioning dosing) is ongoing.

Clinical trial identification

NCT02592577

NCT02989064

Editorial Acknowledgement

Editorial support will be provided by Envision Pharma

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