Immatics reports interim clinical data from ongoing Phase 1b Cohort A

Immatics announced an interim clinical data update for 11 patients with recurrent and/or refractory solid cancers treated with ACTengine IMA203 TCR-T monotherapy in the ongoing Phase 1b dose expansion Cohort A. IMA203 TCR-T cells are directed against an HLA-A*02-presented peptide derived from PRAME, a broadly expressed solid cancer target with clinical proof-of-concept for IMA203 demonstrated by Immatics in 2022. Overall, IMA203 showed a high rate of deep and durable objective responses, with a confirmed objective response rate of 67%, across multiple tumor types, including two confirmed partial responses, cPR, ongoing at more than 9 months after treatment and three additional partial responses ongoing at data cut-off. IMA203 monotherapy continues to be well tolerated in heavily pre-treated patients at doses of up to approximately 9 billion CD8+ TCR-T cells. No high-grade cytokine release syndrome, CRS, and no immune effector cell associated neurotoxicity syndrome, ICANS, were observed in Cohort A at data cut-off. Safety data for IMA203 TCR-T monotherapy in Phase 1b Cohort A: Treatment with IMA203 monotherapy continues to show manageable tolerability at doses as high as ~9×109 TCR-T cells. At data cut-off on April 4, 2023, 11 PRAME-positive patients were infused with IMA203 TCR-T cells at dose level 4 or DL5 with a mean total infused dose of 3.67×109 TCR-T cells. Based on data review of 6 patients in the exploratory highest DL5, this DL was cleared by the DSMB for safety, and the updated provisional recommended Phase 2 dose now includes DL4 and DL5. The final RP2D will be defined prior to starting Phase 2. Most frequent treatment-emergent adverse events were as expected for cell therapies. All 11 patients experienced expected cytopenia associated with lymphodepletion. 10 patients had a low to moderate cytokine release syndrome, of which 5 patients had Grade 1, and 5 patients had Grade 2 CRS. No high-grade CRS and no immune effector cell associated neurotoxicity syndrome were observed in any of these 11 patients. No dose-dependent increase of CRS was observed across Phase 1a and Phase 1b Cohort A. At data cut-off on April 4, 2023, 11 patients were infused with IMA203 TCR-T cells and evaluable for at least one tumor response assessment post treatment. Objective responses were observed in last-line solid cancer patients including cutaneous melanoma, ovarian cancer, uveal melanoma, head and neck cancer, synovial sarcoma. Initial objective response rate of 64% was observed at ~week 6. Confirmed ORR of 67% was observed at ~month 3; initial responses at week 6 were confirmed for all 6 responders with available subsequent 3-month scan. Median duration of response was not reached at a median follow-up3 of 8.5 months. Immatics believes, the results presented today further validate PRAME as one of the most promising solid tumor targets for TCR-based therapies. Immatics’ IMA203 development strategy is based on two pillars aimed initially at a fast-to-market approach and, later at a broad development. As a second step, Immatics plans to also expand development to other cancer types, such as uterine cancer, lung cancer, breast cancer, head and neck cancer and other tumor types having a broad patient reach. An update on all three IMA203 Phase 1b Cohorts and clinical development path for PRAME TCR-T monotherapy towards registration-directed trials and potential commercialization is planned for 4Q 2023.