Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

6072 - Initial Safety Assessment of MAGE-A4 SPEAR T-cells

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Clinical Research

Tumour Site

Presenters

David Hong

Citation

Annals of Oncology (2018) 29 (suppl_8): viii400-viii441. 10.1093/annonc/mdy288

Authors

D.S. Hong1, M.O. Butler2, M. Johnson3, A.J. Olszanski4, E. Norry5, E. Van Winkle5, K.D. Chagin6, R.G. Amado6

Author affiliations

  • 1 Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 77035 - Houston/US
  • 2 Medical Oncology, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 3 Oncology, Sarah Cannon Research Institute, Tennessee Oncology, Nashville/US
  • 4 Department Of Hematology/oncology, Fox Chase Cancer Center, 19111-2497 - Philadelphia/US
  • 5 Clinical, Adaptimmune, 19112 - Philadelphia/US
  • 6 Clinical, Adaptimmune LLC, 19103 - Philadelphia/US
More

Resources

Abstract 6072

Background

This ongoing study (NCT03132922) evaluates the safety and tolerability of genetically engineered autologous specific peptide enhanced affinity receptor (SPEAR) T-cells (MAGE-A4c1032T cells) directed towards a MAGE-A4 peptide expressed on tumors in the context of HLA-A*02.

Methods

This first-in-human T-cell dose-escalation study utilizes a modified 3 + 3 design to evaluate safety, including dose-limiting toxicities (DLT). Patients who are HLA-A*02 positive (excluding *02:05 and *02:07) and have inoperable or metastatic (advanced) NSCLC, urothelial cancer, melanoma, synovial sarcoma, MRCLS, squamous cell head and neck, ovarian, gastric or esophageal tumors with MAGE-A4 expression and meet all other entry criteria are eligible for treatment. Following apheresis, T-cells are isolated, transduced with a lentiviral vector containing the MAGE-A4c1032TCR, and expanded. Prior to transduced cell infusion, patients are given lymphodepleting chemotherapy (Flu 30 mg/m2/d and Cy 600 mg/m2/d, on days -7, -6 and -5 in dose groups 1 and 2, and additional Flu 30 mg/m2/d on day -4 in dose group 3). Groups 1, 2 and 3 will consist of 3-6 patients, and transduced cell doses will be as follows: 0.1 × 109 (±20%), 1 × 109 (range: 0.5 – 1.2 × 109), and 5 × 109 (range: 1.2 – 6 × 109), respectively. The DLT observation period is the first 30 days following the infusion of SPEAR T-cells for each patient in all groups. Following dose escalation, up to 30 patients will be enrolled at 5 x 109 (range: 1.2 x 109 -10 x 109).

Results

3 patients were treated with 0.1 × 109 MAGE-A4 SPEAR T-cells, and transduced cells are detectable in peripheral blood. AEs for the first 2 patients reported at grade (G) ≥3 include anemia, hypoglycemia, hyponatremia, lymphopenia, neutropenia, and thrombocytopenia. Serious AEs included G4 hyponatremia, G3 atrial fibrillation, G3 syncope (unrelated to T-cell therapy), G1 CRS and G2 encephalopathy syndrome (both related), and G2 generalized muscle weakness (possibly related). None of the events were considered DLTs by the Safety Review Committee.

Conclusions

MAGE-A4 SPEAR T-cells at the 0.1 × 109 transduced cell dose appear to show no evidence of on-target or off-target toxicity. Preliminary data support continued investigation of the TCR, and this trial is ongoing. Updated safety data will be presented.

Clinical trial identification

NCT03132922.

Legal entity responsible for the study

Adaptimmune.

Funding

Adaptimmune.

Editorial Acknowledgement

Editorial assistance was provided by Envision Pharma.

Disclosure

E. Van Winkle, K.D. Chagin, R.G. Amado: Employee: Adaptimmune. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.