Abstract 157P
Background
ImmTAC® bispecific proteins redirect polyclonal T cells to target intra/extracellular proteins using a T cell receptor as targeting domain. IMC-C103C (MAGE-A4 × CD3) is an ImmTAC against MAGE-A4, which is expressed in several tumors including ovarian carcinoma (OC). ≥ 90 μg IMC-C103C was demonstrated as the clinically active range (Davar 2021). Pre-selection for MAGE-A4 expression was not required as a majority of OC express MAGE-A4 (H score ≥ 1) and tebentafusp demonstrated OS benefit and ctDNA reductions regardless of H score, although RECIST responses were enriched at higher H scores (Leach 2021).
Methods
HLA-A*02:01+ OC pts were enrolled as all-comers in escalation and expansion cohorts with MAGE-A4 expression tested by IHC retrospectively. Ph1 primary objective is to identify expansion dose. Other objectives: adverse events (AE), ORR (RECIST v1.1), OS and biomarkers including ctDNA (Guardant 360).
Results
As of 24Jun2022, 31 heavily pretreated OC pts (87% platinum resistant) received 90 - 240 μg IMC-C103C. Of 28 OC pts with evaluable MAGE-A4 IHC expression, 16 (57%) were positive (pos) with median H score 28 (maximum 300). 12/28 (43%) pts had H score = 0 (neg). Only 1 pt had H score > 130. The AE profile is consistent with previously reported (Davar 2021). Most common related AEs were pyrexia (68%), chills (52%), and CRS (45%), the vast majority were Grade 1/2. No related AEs resulted in treatment discontinuation or death. 27 of 31 were response evaluable. 15 pts were MAGE-A4 pos; 1 had confirmed PR (duration 12+ months) and 5 had SD. 6/15 pts had any tumor shrinkage. Of 12 MAGE-A4 neg/unknown (unk) pts, 1 had SD and 1 had any tumor shrinkage. Of 21 ctDNA evaluable pts, 4/11 MAGE-A4 pos and 1/10 MAGE-A4 neg/unk had ≥ 50% ctDNA reduction. After first dose, serum IFNγ and TNFα were not induced in MAGE-A4 neg pts or minimally induced in MAGE-A4 pos pts, consistent with mostly low H scores.
Conclusions
When enrolled as all-comers, the vast majority of heavily pre-treated OC pts had either zero or very low MAGE-A4 expression. IMC-C103C is clinically active but the low MAGE expression may have resulted in few RECIST responses. Dose optimization and signal detection continue in MAGE-A4 pos pts with additional tumor types.
Clinical trial identification
NCT03973333.
Legal entity responsible for the study
Immunocore Ltd.
Funding
Immunocore Ltd and Genentech.
Disclosure
R. Sweis: Financial Interests, Personal, Advisory Board: Aduro, Astellas, AstraZeneca, BMS, EMD serono, Editas, Exelixis, Eisai, Janssen, Mirati, Pfizer, Silverback, Seattle Genetics; Financial Interests, Personal, Invited Speaker: Aveo; Financial Interests, Institutional, Invited Speaker: AbbVie, Aduro, Ascendis, Bayer, BMS, CytomX, Eisai, Genentech/Roche, Immunocore, Novartis, Merck, Mirati, Moderna, QED, Astellas; Financial Interests, Institutional, Research Grant: Epivax. E. Garralda: Financial Interests, Personal, Advisory Board: Genentech, F.Hoffmann/La Roche, Neomed Therapeutics1 Inc, Boehringer Ingelheim, Janssen Global Services, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Lilly, Hengrui; Financial Interests, Personal, Invited Speaker: Ellipses Pharma, Seattle Genetics, Bristol Mayers Squibb, MSD, F-Star Therapeutics; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho. O. Saavedra Santa Gadea: Financial Interests, Personal, Other, Travel/Accomodation/Expense: Affimed. K.N. Moore: Financial Interests, Personal, Advisory Board: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Eisai, EMD Serono, GSK/Tesaro, Genentech/Roche, Hengrui, Immunogen, IMab, Mereo, Myriad, Caris, Mersana, Novartis, Novocure, OncXerna, OncoNova, Tarveda, VBL Therapeutics; Financial Interests, Personal, Full or part-time Employment: GOG Partners Associate Director; Financial Interests, Institutional, Full or part-time Employment: NRG Ovarian Cancer Chair; Financial Interests, Personal, Royalties: UP to Date; Financial Interests, Institutional, Invited Speaker, international CO-PI, local site PI: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Immunogen, GSK/Tesaro, Lilly, PTC Therapeutics, Daiichi Sankyo, Regeneron, Artios, Bolt, verastem; Non-Financial Interests, Personal, Invited Speaker: GOG. D. Davar: Financial Interests, Institutional, Research Grant: Arcus, BMS, Checkmate Pharmaceuticals, CellSight Technologies, Merck, Tesaro/GSK; Financial Interests, Personal, Advisory Role: Checkmate Pharmaceuticals, Shionogi, Vedanta CE; Financial Interests, Personal, Other, US Patent 63/124,231, Dec 11, 2020; Patent 63/208,719, June 9, 2021: Intellectual Property. 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. N.H. Segal: Financial Interests, Personal, Advisory Board: Immunocore, PsiOxus, Roche/Genentech, Boehringer Ingelheim, Revitope, ABL Bio, Novartis; Financial Interests, Institutional, Research Grant: Regeneron, Immunocore, Incyte, AstraZeneca, BMS, Merck, Pfizer, Roche/Genentech. T.R.J. Evans: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bicycle Therapeutics, Bristol Myers Squibb, Clovis, Eisai, Medivir, MSD, Nucana, Roche/ Genentech; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Medivir, MSD, Nucana, Roche/ Genentech; Financial Interests, Personal, Other, Support to attend international conferences: Bayer, Bristol Myers Squibb, Celgene, MSD, Nucana, Pierre Fabre, Roche/ Genentech; Financial Interests, Institutional, Principal Investigator, Coordinating PI, reimbursement of study costs for commercial studies: Adaptimmune, Bristol Myers Squibb, Eisai, iOnctura, MSD, Nucana, Sanofi; Financial Interests, Institutional, Principal Investigator, Local PI, reimbursement of study costs for commercial studies: Astellas, Basilea, Bayer, Beigene, Bicycle Therapeutics, Boehringer Ingelheim, Celgene, Codiak, CytomX, GSK, Immunocore, Johnson & Johnson, Lilly, Medivir, MiNa Therapeutics, Novartis, Pfizer, Roche, Sapience Therapeutics, Seagen, Sierra, Starpharma, UCB; Financial Interests, Institutional, Principal Investigator, Educational grant for investigator-led study and reimbursement of study costs for commercial studies: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Support for non-commercial investigator-led study: Verastem; Non-Financial Interests, Personal, Other, Member of Clinical Experts Review Panel / Clinical Research Committee: Cancer Research UK; Non-Financial Interests, Personal, Other, Annual Meeting abstracts committee: International Liver Cancer Association; Non-Financial Interests, Personal, Other, Member of Scientific Advisory Panel: Pancreatic Cancer Research Fund; Non-Financial Interests, Personal, Member: America Association for Cancer Research, American Society of Clinical Oncology, Association of Cancer Physicians (UK), British Association for Cancer Research, European Association for Cancer Research, International Liver Cancer Association; Other, Personal, Other, Clinical Subjects Editor: British Journal of Cancer; Other, Personal, Other, Chair of Independent Data Monitoring Committee- honorarium payable to the employing institution: Genmab. M. Dar, Y. Yuan: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. L. Collins, P.B. Kirk: Financial Interests, Personal, Stocks/Shares: Immunocore; Financial Interests, Personal, Full or part-time Employment: Immunocore. O. Karakuzu: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. J.S. Lopez: Financial Interests, Institutional, Research Grant: Roche-Genentech, Basilea, Genmab; Financial Interests, Personal, Advisory Board: Basilea, Ellipses. I. Melero: Financial Interests, Personal, Advisory Board: Gossamer Bio, Highlight Therapeutics, MSD, Alligator Bioscience, Genmab, Numab, NOXXON Pharma AG, BMS, CRISPR Therapeutics, Genentech, AstraZeneca, Boehringer Ingelheim, EMD Serono, Roche, CatalYm GmbH, BioLineRx, Boston Pharma, Janssen, Hookipa Pharma, HotSpot Therapeutics, Inc., ImmuneSensor Therapeutics, Inc., Monopteros Therapeutics; Financial Interests, Personal, Other, Consultant: Pharma Mar; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, BMS, Genmab, Alligator.