Data from the IMA203 trial were presented at the SITC 2021 annual meeting.
IMA203, an autologous, TCR-engineered T cell (TCR-T), PRAME-directed therapy, has shown efficacy across multiple types of solid cancers.1
Positive data from the IMA203 phase 1 trial (NCT03686124) were presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021. Investigator Martin Wermke, MD, University Hospital Dresden, and colleagues assessed the adoptive cell therapy in patients with solid cancers.
“We observed multiple clinical responses early-on during dose escalation and saw anti-tumor activity at much lower doses than would have been expected in the field of TCR-T. IMA203 T cells will now be tested at the target dose level and have the potential to provide meaningful benefits to patients with advanced stages of cancer,” Wermke, who is a coordinating investigator of Immatics’ ACTengine® trials in Germany and head of the Early Clinical Trial Unit of the National Center for Tumor Diseases at the University Hospital Carl Gustav Carus in Dresden, Germany, said in a statement.2
The ongoing, dose-escalation, phase 1 trial is enrolling patients with HLA-A*02:01- and PRAME-positive relapsed/refractory solid tumors unresponsive to available standard treatments. The trial is primarily assessing the safety and tolerability of IMA203. Secondary outcomes include molecular and immunological measures to evaluate anti-tumor activity and pharmacodynamics.
After leukapheresis, an autologous TCR-T product is manufactured for each participant. The T cells are infused after lymphodepletion with fludarabine and cyclophosphamide. Participants are also treated with low-dose IL-2.
The trial has dosed 16 heavily pre-treated patients across dose levels as of August 15, 2021. Doses ranged from 0.08 to 0.81x109 transduced CD8 T cells per patient, levels of which have not led to anti-tumor responses in other TCR-T trials.
IMA203 seemed to be well-tolerated, with only transient and manageable treatment-emergent adverse events (AEs). Among AEs were cytopenias of grade 1-4, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome (ICANS) of grade 1 and 2, and 1 dose-limiting toxicity in the second dose level.
In terms of efficacy, all 12 evaluable patients achieved disease control, defined as stable disease (SD) or a partial response (PR), with 6 patients demonstrated PRs according to RECIST1.1. Two PRs were confirmed. At dose level 1 (median dose, 0.11x109), all three patients achieved SD. Beyond dose level 1 (median dose, 0.30x109), 6 of 9 patients experienced a PR.
Responses were seen across solid cancer types, including synovial sarcoma (N=3), malignant melanoma (N=2) and head and neck cancer (N=1). Investigators also observed robust T cell engraftment was in all patients and tumor infiltration by TCR-modified T cells in patients with evaluable on-treatment biopsies.
“To our knowledge, IMA203 is the first TCR-T product candidate that induced frequent tumor responses across multiple solid cancers using transduced T cells at doses below 1 billion and has a manageable safety profile,” Wermke and colleagues concluded.1 Next steps are to assess rates and durability of response at higher dose levels.
“The unexpected high clinical response rate in PRAME-positive patients before reaching our target cell dose has shifted our expectations of what cell therapy could potentially achieve in solid cancers. This is a very promising first step, which encourages us to double down efforts for a focused development strategy of our programs targeting PRAME,” Cedrik Britten, MD, chief medical officer, Immatics, added to the statement.2 “Our immediate next steps aim to maximize the benefit for PRAME-positive patients through (1) ACTengine® IMA203 monotherapy at target dose, (2) combination with checkpoint inhibitors, and (3) our efficacy-enhanced next-gen TCR-T approach ACTengine® IMA203CD8. In addition, we are gearing up for clinical testing of our off-the-shelf Bispecifics program, TCER® IMA402 targeting PRAME, which has the potential of delivering transformational benefits for patients, combined with the advantages of easy and fast supply at significantly reduced cost of goods.”
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