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.
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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.”
For more coverage of SITC 2021, click here.