1001MO - Initial safety, pharmacokinetics, and anti-tumor activity data of TCER IMA401, a MAGEA4/8-directed half-life extended TCR bispecific, in phase I dose escalation

Background

T cell-engaging bispecifics are designed to redirect T cells to cancer antigens. IMA401 is a next-gen T cell engaging receptor (TCER®) combining a high-affinity TCR domain against an HLA-A*02:01-presented MAGEA4/8 peptide, a low-affinity T cell-recruiting antibody and an Fc part for half-life extension. The target peptide exhibits a >5-fold higher density compared to the MAGEA4-derived peptide targeted by other bispecifics or cell therapies.

Methods

This ongoing Phase 1a/1b first-in-human clinical trial evaluates IMA401 in patients (pts) with recurrent/refractory solid tumors. HLA-A*02:01+ and MAGEA4/8+ pts received initially QW then Q2W iv. IMA401 infusions. Primary objectives: MTD and/or RP2D. Secondary objectives: safety, tolerability, PK, initial anti-tumor activity.

Results

As of April 1, 2024, 25 heavily pretreated cancer pts received IMA401 across the first dose levels (DL1-7, 6.6μg-2.5mg). IMA401 showed manageable tolerability with most common (≥30%) treatment-related adverse events being transient lymphopenia (G1-4) and CRS (G1/2). High-grade (G3/4) neutropenia observed at DL7 did not reoccur after the introduction of dexamethasone pre-treatment. MTD/RP2D was not reached and dose escalation is ongoing. Median terminal half-life was 15.0 days. 55% (11/20) of efficacy-evaluable pts treated in the escalation phase, including initial low MABEL-based starting DLs, achieved disease control (SD/PR). Among these were pts with ovarian cancer, sqNSCLC, gastric cancer, HNSCC, melanoma, and neuroendocrine carcinoma. 45% (9/20) of the pts showed shrinkage of target lesions (median -21.7%), including 3 pts with durable confirmed PRs at 4+, 10+ and 11+ months after first infusion.

Conclusions

IMA401 was well tolerated and its single-agent anti-tumor activity was demonstrated by durable objective responses and disease control. The prolonged half-life prompted a switch to treatment every 2 weeks already during dose escalation. The data of this ongoing Phase 1 dose escalation trial provide first clinical PoC for the next-gen half-life extended TCER® format and its potential in multiple solid tumors.

Clinical trial identification

NCT05359445.

Editorial acknowledgement

Legal entity responsible for the study

Immatics Biotechnologies GmbH.

Funding

Immatics Biotechnologies GmbH.

Disclosure

M. Wermke: Financial Interests, Personal, Advisory Board: Novartis, Boehringer Ingelheim, Bayer, Bristol Myers Squibb, ImCheck Therapeutics, Immatics, Pfizer, AstraZeneca, Tacalyx GmbH, Regeneron, Zymeworks, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Synlab GmbH, Janssen, EMD Merck Serono, GWT TUD GmbH, Amgen, Novartis; Financial Interests, Personal, Other, Member of DSMC: ISA Therapeutics; Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Other, Congress Travel Cost Support: AstraZeneca, EMD Merck Serono, Janssen, Boehringer Ingelheim, Immatics, Daiichi Sankyo, Iovance. S. Ochsenreither: Financial Interests, Personal, Advisory Board: MSD, BMS, Janssen, Ipsen, Immunocore, Genemab, Pfizer, Pfizer; Financial Interests, Personal, Invited Speaker: MSD, Merck, Immunocore, Janssen; Financial Interests, Personal, Other, Support for travel/meeting: Janssen, Pfizer, Merck; Financial Interests, Personal, Advisory Board, Patent of T cell therapy target: Fred Hutchinson cancer Research Center; Financial Interests, Personal and Institutional, Research Grant: Bayer. S. Gröpper: Financial Interests, Personal, Advisory Board: BMS, Sobi, ngelh. D. Heudobler: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, MSD; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Roche, AbbVie; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi, AbbVie, Bristol Myers Squibb, Janssen-Cilag; Financial Interests, Institutional, Funding: Janssen-Cilag, Bristol Myers Squibb. D. Jäger: Non-Financial Interests, Institutional, Advisory Board: Roche Pharma AG, OncoOne Research & Development Research GmbH, Amgen, CureVac AG, MSD, Definiens, F. Hoffmann-La Roche Ltd., VAXIMM AG, Oncolytics Biotech Inc., Genmab A-S., Life Science Inkubator GmbH; Non-Financial Interests, Institutional, Invited Speaker: AstraZeneca GmbH, GRN Klinik Weinheim, BMS GmbH & Co KG, MSD, If-Kongress Management GmbH, Gruppe 5 Filmproduktion GmbH, The Norwegian Cancer Society, Dept. of Radiation Medicine, Univ. of Kentucky, Centrum für integrierte Onkologie Bonn; Non-Financial Interests, Institutional, Leadership Role: BMS Stiftung Immunonkologie. A. Bleckmann: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen-Cilag, Merck, Mirati, MSD, Novartis, Pfizer, Roche, Sanofi, Servier, Takeda, Art Tempi, StreamedUp; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen-Cilag, Merck, Mirati, MSD, Novartis, Pierre-Fabre, Pierre-Fabre, Pfizer, Roche, Sanofi, Servier, Takeda, StreamedUp, Onkowissen.TV; Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen-Cilag, Merck, Mirati, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sanofi, Servier, Takeda; Financial Interests, Institutional, Invited Speaker: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen-Cilag, Merck, Mirati, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sanofi, Servier, Takeda, Art Tempi, Onkowissen.TV; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Leadership Role: AIO. J.S. Hecker: Non-Financial Interests, Institutional, Principal Investigator: Immatics; Non-Financial Interests, Institutional, Sponsor/Funding: Immatics. S. Bunk: Financial Interests, Personal, Full or part-time Employment: Immatics Biotechnologies GmbH, Tübingen, Germany; Financial Interests, Personal, Stocks/Shares: Immatics Biotechnologies GmbH, Tübingen, Germany. N. Hilf: Financial Interests, Personal and Institutional, Full or part-time Employment: Immatics; Financial Interests, Personal and Institutional, Stocks/Shares: Immatics; Financial Interests, Personal and Institutional, Stocks or ownership: Immatics; Financial Interests, Personal and Institutional, Leadership Role: Immatics. M. Hutt: Financial Interests, Institutional, Licencing Fees or royalty for IP: Immatics; Financial Interests, Institutional, Stocks/Shares: Immatics. A. Mayer-Mokler: Financial Interests, Personal and Institutional, Full or part-time Employment: Immatics; Financial Interests, Personal and Institutional, Stocks/Shares: Immatics. S. Missel: Financial Interests, Personal, Full or part-time Employment: Immatics Biotechnologies; Financial Interests, Personal, Stocks/Shares: Immatics Biotechnologies; Non-Financial Interests, Project Lead: Immatics Biotechnologies. O. Veremchuk: Financial Interests, Institutional, Full or part-time Employment: Immatics Biotechnologies GmbH; Financial Interests, Institutional, Full or part-time Employment, Former employee: PRA, Quintiles. C. Britten: Financial Interests, Personal, Officer, Chief Medical Office of Immatics Biotechnologies N.V. and its US subsidiary Immatics US Inc: Immatics Biotechnologies; Financial Interests, Personal, Stocks/Shares, Owner of shares and options: Immatics Biotechnologies. C. Reinhardt: Financial Interests, Institutional, Officer, Chief Development Officer: Immatics; Financial Interests, Institutional, Ownership Interest: Immatics. All other authors have declared no conflicts of interest.