728O - Results from phase I dose escalation of IMC-F106C, the first PRAME × CD3 ImmTAC bispecific protein in solid tumors

Background

IMC-F106C is the first TCR bispecific protein targeting CD3 and PRAME, the most broadly expressed cancer testis antigen, which is homogenously expressed in multiple tumors (eg, lung, ovarian, endometrial, melanoma, breast). ImmTAC bispecifics redirect polyclonal T cells to target intra/extracellular cancer proteins, as validated by tebentafusp (tebe; gp100×CD3 ImmTAC) with an overall survival benefit in metastatic uveal melanoma (mUM).

Methods

HLA-A*02:01+ patients (pts) with selected advanced tumors are eligible. Prospective PRAME testing required in low PRAME prevalence tumors. Primary objectives: safety and recommended dose. Secondary/exploratory objectives: efficacy, biomarkers and ctDNA response. IMC-F106C is dosed weekly with extended monitoring for intra-patient dose escalation during first 3 wks until target dose (TD).

Results

As of April 2022, 42 heavily pre-treated pts, across tumor types, were treated in 9 cohorts (TD 0.3-160 mcg) during dose escalation. 86% of tumors were confirmed PRAME+, median H score = 203. Most common (>30%) related AEs were consistent with the mechanism of action: pyrexia 64%; cytokine release syndrome (CRS) 45%; hypotension, fatigue 38% each; chills 36%; and nausea 33%. These were mostly Grade (G) 1/2, occurred in first 3 wks and rapidly resolved. 31% pts had related G3/4 AEs, most commonly lymphopenia 14% and AST increase 7%. There were no G3/4 CRS, treatment related discontinuations or deaths. Confirmed PRs were seen at TD of ≥ 20 mcg, a threshold dose for consistent and robust T cell activation. 18 pts at ≥ 20mcg were confirmed PRAME+, including 5 mUM pts who progressed on prior tebe. In 13 tebe-naïve pts, 69% (9/13) had tumor shrinkage and 38% (5/13) had a partial response (PR) including 2 of 3 cutaneous melanoma (all failed prior anti-PD1 & CTLA4), 1 of 2 ovarian, 2 of 5 mUM. All PRs are confirmed, 4 PRs ongoing. ctDNA response was observed across multiple tumor types and included some pts with complete clearance.

Conclusions

IMC-F106C, the first PRAME×CD3 ImmTAC, is well tolerated and demonstrated durable RECIST partial responses and ctDNA response in PRAME+ pts across multiple tumor types. Dose escalation and multiple expansions are ongoing.

Clinical trial identification

NCT04262466.

Editorial acknowledgement

Legal entity responsible for the study

Immunocore Ltd.

Funding

Immunocore Ltd.

Disclosure

O. Hamid: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Pfizer, Sanofi / Regeneron; Financial Interests, Personal, Advisory Board: Aduro, Akeso, Amgen, Beigene, BMS, Roche Genentech, GSK, Immunocore, Idera, Incyte, Janssen, Merck, Nextcure, Novartis, Pfizer, Sanofi / Regeneron, Seagen, Tempus, Zelluna, Bioatla, Alkermes, Instil Bio, Iovance; Financial Interests, Institutional, Invited Speaker: Arcus, Aduro, Akeso, Amgen, Bioatla, BMS, CytomX, Exelixis, Roche Genentech, GSK, Immunocore, Idera, Incyte, Iovance, Merck, Moderna, Merck Serono, Nextcure, Novartis, Pfizer, Sanofi / Regeneron, Seagen, Torque, Zelluna, Rubius. T. Sato: Financial Interests, Personal, Advisory Role: Immunocore, Castle Biosciences; Financial Interests, Institutional, Research Grant: Immunocore, Verastem; Financial Interests, Personal, Expenses: CastleBioscience. D. Davar: Financial Interests, Institutional, Research Grant: Arcus, BMS, Checkmate Pharmaceuticals, CellSight Technologies, Merck, Tesaro/GSK; Financial Interests, Personal, Consultant: Checkmate Pharmaceuticals, Shionogi, Vedanta CE; Financial Interests, Personal, US Patent 63/124,231 / US Patent 63/208,719: Patent office. M.K. Callahan: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, ImmunoCore, AstraZeneca; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. F. Thistlethwaite: Financial Interests, Personal, Advisory Board, honoraria: Bayer; Financial Interests, Personal, Advisory Board, Ad board: BMS, Zelluna; Financial Interests, Personal, Advisory Board, Ad boards: GSK; Financial Interests, Personal, Advisory Board, Adboard/consultancy: Tknife; Financial Interests, Personal, Advisory Board: Adicet, Janssen, EnaraBio, Immatics, Ixaka; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, iMATCH is a 12 partner consortium funded by not for profit Innovate UK (UK government body) partners include commercial, clinical and academic institutes. I am director and my salary (0.2WTE) is supported through this work as a grant to my institution (The Christie NHS foundation trust - not for profit NHS hospital) from IUK: iMATCH director; Financial Interests, Institutional, Officer, Clinical lead for this 10 partner consortium of clinical academic and commercial partners. My salary is partly supported (approx. 0.05WTE) through this by a grant paid by Innovate UK (a NFP government body) to my institution (The Christie NHS foundation trust a NFP UK hospital): SAMPLE; Financial Interests, Institutional, Invited Speaker: Pfizer, GenMab, synthon, CytomX, Incyte, Janssen, Adaptimmune, Aveo, BMS, GSK, Roche, AbbVie, Immunocore, Achilles ltd, Agalimmune Ltd, Kymab Ltd, Chugai, Millenium Pharmaceuticals/Takeda, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Panel Member for a Funding Committee (MRC is a UK government NFP organisation): MRC DPFS Panel Member. R. Aljumaily: Financial Interests, Personal, Advisory Role: Regeneron, AstraZeneca. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Bioscience, Array Biopharma, Artios Pharma, AstraZeneca, Atreca, Beigene, BerGenBio, BioAtla, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, Erasca, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi , Seven and Eight Biopharmaceuticals / Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics; Financial Interests, Institutional, Advisory Role: AbbVie, Achilles Therapeutics, Amgen, AstraZeneca, Axelia Oncology, Atreca, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, EMD Serono, G1 Therapeutics, Genentech / Roche, Genmab, GlaxoSmithKline; Financial Interests, Institutional, : Gritstone Oncology. H. Arkenau: Financial Interests, Personal, Invited Speaker: Servier, Guardant; Financial Interests, Personal, Advisory Board: iOnctura, Beigene; Financial Interests, Institutional, Invited Speaker: multiple small and large Pharma/Biotechs. E.E. Ileana Dumbrava: Financial Interests, Institutional, Grant: Bayer HealthCare Pharmaceuticals Inc, Immunocore Ltd, Amgen, NCI, Aileron Therapeutics, Compugen Ltd, TRACON Pharmaceuticals Inc, Unum Therapeutics, Immunomedics, BOLT Therapeutics, Aprea Therapeutics, Bellicum Pharmaceuticals, PMV Pharma, Triumvira, Seagen Inc, Mereo BioPharma 5 Inc, Sanofi, Astex Therapetics ; Financial Interests, Personal, Advisory Board: BOLT Therapeutics, Mersana; Financial Interests, Personal, Advisory Role, Consultant: Catamaran Bio. B. Izar: Personal, Advisory Role: Immunocore. S. Marshall: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. Y. Yuan: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. M. Deo: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. S. Stanhope: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. L. Collins: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. R. Mundy: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. S.E. Abdullah: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. J.S. Lopez: Financial Interests, Personal, Research Grant: Roche Genentech, Basilea, Genmab; Financial Interests, Personal, Advisory Board: Basilea, Ellipses. All other authors have declared no conflicts of interest.