Immatics Presents Phase I Data from ACTolog® Multi-Target Pilot Study IMA101 at the 35th Annual SITC Conference
- Category: DNA RNA and Cells
- Published on Tuesday, 10 November 2020 15:30
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- Multi-target Adoptive Cell Therapy (ACT) with endogenous T cells against defined pHLA targets demonstrates feasibility, tolerability and high T-cell persistence.
- Clinical courses observed in patients indicate COL6A3 exon 6 as a potentially valuable tumor target for continued evaluation.
- The data support further exploration of a multi-target ACT approach using potent T cell receptors (TCRs)
TUEBINGEN, Germany and HOUSTON, TX, USA I November 10, 2020 I Immatics N.V. (NASDAQ: IMTX, “Immatics”), a clinical-stage biopharmaceutical company active in the discovery and development of T cell redirecting cancer immunotherapies, announced today that the Company will present Phase I results from their ACTolog® program IMA101 at the 35th Annual SITC Meeting, held virtually from November 9-14, 2020. 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.
The data will be presented at the Society for Immunotherapy of Cancer (SITC) 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 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).
Immatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer.