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.
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