On November 10, 2020 Immatics N.V. (NASDAQ: IMTX, "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell redirecting cancer immunotherapies, reported that the Company will present Phase I results from their ACTolog program IMA101 at the 35th Annual SITC (Free SITC Whitepaper) Meeting, held virtually from November 9-14, 2020 (Press release, Immatics, NOV 10, 2020, View Source [SID1234570501]). ACTolog is a pilot study for a personalized multi-TCR-T approach that aims to address current challenges for effective cancer immunotherapy, such as tumor heterogeneity and tumor immune escape. The data to be presented demonstrate the feasibility of the approach while also showing the therapy is well tolerated. In addition, case studies within the treated patient population support further exploration of a personalized ACT approach using potent high-affinity TCRs.
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The data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting on November 11.
Clinical Data Highlights
14 patients with relapsed/refractory solid tumors received adoptive cell therapy IMA101 directed against defined pHLA targets specific to each patient
ACTolog demonstrates feasibility of a multi-target multi-T cell product approach
The target positivity rate of 90% demonstrated that such a multi-target approach leads to minimal patient attrition during screening due to lack of target expression.
Each product combination in the ACTolog multi-target approach was guided by confirmed target expression in patient-derived biopsies.
ACTolog was well-tolerated in heavily pretreated patients
Common adverse events included expected cytopenias, mostly associated with the lymphodepleting regime and in many cases accompanied by Grade 1-2 cytokine release syndrome.
ACTolog shows remarkable T cell persistence and tumor infiltration
ACTolog treatment resulted in high target-specific T cell levels and persistence with total frequencies up to ~80% of all peripheral CD8+ T cells in the blood.
Target-specific T cells were detectable in post-treatment tumor biopsies.
Individual TCRs in the endogenous T cell products showed a broad range of avidities, however the majority being of low avidity, reflecting the range to be expected in the natural immune repertoire.
ACTolog revealed long-term disease stabilization in some patients
All three patients with prolonged disease stabilization showed high frequency of target-specific T cells (>40% of CD8+ T cells) in the blood post-infusion.
Two of these three patients received a COL6A3 exon 6-specific T cell product indicating COL6A3 as a potentially valuable tumor target and targeting the tumor stroma as a promising approach.
ACTolog results warrant the further evaluation of a multi-target ACT approach using potent high-avidity TCRs (i.e. autologous TCR-engineered T cells)
"We are excited to present the final results of this personalized adoptive cell therapy against multiple novel defined peptide-HLA cancer targets at SITC (Free SITC Whitepaper) 2020," said Apostolia Tsimberidou, M.D., Ph.D., Lead Investigator of the study and Professor, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center. "The target positivity rate of 90% among HLA-A*02:01 positive patients highlights that this approach can be applied to a variety of cancer patients. In addition, we were able to show that the treatment approach was feasible and, overall, well tolerated. Most notably, three out of 14 patients had prolonged disease stabilization lasting well over six months. We believe that these results warrant the further evaluation of a multi-target adoptive cell therapy approach using potent high-avidity TCRs possibly combined with other immunotherapeutic interventions to solidify patient responses over time."
"To our knowledge the ACTolog pilot study is the first trial to demonstrate feasibility of an actively personalized T cell therapy approach directed against multiple targets. Moreover, it supports that targeting COL6A3 exon 6 represents a promising approach to tackling the tumor stroma," remarked Harpreet Singh, CEO of Immatics. "The low avidity of the patients’ own TCR repertoire that we have seen in the study population, however, demonstrates the need for more potent TCRs to enable greater therapeutic impact for cancer patients. Our ACTengine approach, evaluated currently in three ongoing clinical trials, is specifically addressing this aspect by genetically engineering T cells with highly potent TCRs. We look forward to providing the first clinical data on the ACTengine trials in the first quarter of 2021."
The full poster is available on Immatics’ website using this link.
About Immatics’ ACTolog Program
The ACTolog trial (IMA101-101) is a clinical pilot trial to demonstrate tolerability and feasibility of a multi-target ACT approach. The ACTolog concept is based on selecting and expanding a patient’s own autologous T cells dependent on the detection of ACTolog targets in the patient’s tumor tissue. The ACTolog approach was designed as the first known multi-target precision immunotherapy delivering a proof-of-principle for a next-generation multi-TCR-T approach using highly potent TCRs as in Immatics’ lead product class ACTengine (TCR-T).
More information on the clinical trials can be found at the following links: www.immatics.com/clinical-programs and www.clinicaltrials.gov.