91P Phase I dose escalation of IMC-C103C, a CD3×MAGE-A4 T-cell receptor (TCR) bispecific protein
2021; Elsevier BV; Volume: 32; Linguagem: Inglês
10.1016/j.annonc.2021.10.109
ISSN1569-8041
AutoresDiwakar Davar, Randy F. Sweis, George Blumenschein, Rodolfo Gutierrez, Ignacio Melero, H.A. Chen, Fiona Thistlethwaite, Kathleen N. Moore, Neil H. Segal, Elena Garralda, Breelyn A. Wilky, H-T. Arkenau, T.R. Jeffry Evans, Melissa L. Johnson, M. Dar, Christopher J. Holland, Sylwia Marshall, Sarah Stanhope, Peter Kirk, Juanita Lopez,
Tópico(s)Cancer Research and Treatments
ResumoBackgroundTCR bispecific proteins (bsp) redirect polyclonal T cells to target intra/extracellular proteins in cancer, as validated by tebentafusp (CD3×gp100 TCR) with a survival benefit in metastatic uveal melanoma (HR 0.51). IMC-C103C is a TCR bsp against MAGE-A4, a cancer-testis antigen expressed in several tumor types (eg, lung, ovarian, HNSCC, GEJ) but minimally in normal tissue.MethodsHLA-A*02:01+ pts with selected advanced tumors are eligible; prospective MAGE-A4 testing is required in indications with lower MAGE-A4 prevalence. The Ph1 primary objective is to identify the expansion dose. Other objectives: adverse events (AE), clinical activity (RECIST v1.1), biomarkers. IMC-C103C is dosed IV weekly, with step-dosing at > 15 μg (full dose at Day 15).ResultsTable: 91PImmune cell activation markers, day 15-16Day 15 Dose, μgN treated*Blood lymphocytes % decrease, medianSerum IL6 fold increase, medianDetectable IFNg (>LLOD) n/N0.5-4.57Not done1.20/715-6420-605.32/18903-78281/31406-89344/62404-93504/4*40/42 pts treated on Day 15; only 13/18 pts received ≥ 90 μg dose on day 15. Open table in a new tab ConclusionsIMC-C103C is tolerable, demonstrates pharmacodynamic activity consistent with T cell activation (initially at ≥ 15 μg, consistently and robustly at ≥ 90 μg), drives T cells into tumor, and is clinically active. Dose optimization is ongoing.Clinical trial identificationNCT03973333.Legal entity responsible for the studyImmunocore Ltd.FundingImmunocore Ltd.DisclosureD. Davar: Financial Interests, Institutional, Research Grant: Arcus; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Checkmate Pharmaceuticals; Financial Interests, Institutional, Research Grant: CellSight Technologies; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Tesaro/GSK; Financial Interests, Personal, Advisory Role, Consultant: Checkmate Pharmaceuticals; Financial Interests, Personal, Advisory Role, Consultant: Shionogi; Financial Interests, Personal, Advisory Role, Consultant: Vedanta CE; Other, Personal, Other, US Patent 63/124,231, Dec 11, 2020 : US Patent; Other, Personal, Other, US Patent 63/208,719, June 9 2021: US Patent. R.F. Sweis: Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Aduro; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Astellas; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: AstraZeneca; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: EMD Serono; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Exelixis; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Eisai; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Janssen; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Mirati; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Pfizer; Financial Interests, Personal, Advisory Role, Personal fees/Consulting: Seattle Genetics; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Aduro; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CytomX; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Immunocore; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Mirati; Financial Interests, Institutional, Research Grant: Moderna; Financial Interests, Institutional, Research Grant: QED therapeutics. G. Blumenschein Jr.: Financial Interests, Personal, Research Grant, Grant/Contract: Amgen; Financial Interests, Personal, Research Grant, Grant/Contract: Bayer; Financial Interests, Personal, Research Grant, Grant/Contract: Adaptimmune; Financial Interests, Personal, Research Grant, Grant/Contract: Elelixis; Financial Interests, Personal, Research Grant, Grant/Contract: Daiichi Sankyo; Financial Interests, Personal, Research Grant, Grant/Contract: GSK; Financial Interests, Personal, Research Grant, Grant/Contract: Immatics; Financial Interests, Personal, Research Grant, Grant/Contract: Immunocore; Financial Interests, Personal, Research Grant, Grant/Contract: Incyte; Financial Interests, Personal, Research Grant, Grant/Contract: Kite Pharma; Financial Interests, Personal, Research Grant, Grant/Contract: Macrogenics; Financial Interests, Personal, Research Grant, Grant/Contract: Torque; Financial Interests, Personal, Research Grant, Grant/Contract: AstraZeneca; Financial Interests, Personal, Research Grant, Grant/Contract: Bristol Myers Squibb; Financial Interests, Personal, Research Grant, Grant/Contract: Celgene; Financial Interests, Personal, Research Grant, Grant/Contract: Genentech; Financial Interests, Personal, Research Grant, Grant/Contract: MedImmune; Financial Interests, Personal, Research Grant, Grant/Contract: Merck; Financial Interests, Personal, Research Grant, Grant/Contract: Novartis; Financial Interests, Personal, Research Grant, Grant/Contract: Roche; Financial Interests, Personal, Research Grant, Grant/Contract: Xcovery; Financial Interests, Personal, Research Grant, Grant/Contract: Tmunity Therapeutics; Financial Interests, Personal, Research Grant, Grant/Contract: Regeneron; Financial Interests, Personal, Research Grant, Grant/Contract: Beigene; Financial Interests, Personal, Research Grant, Grant/Contract: Repertoire Immune Medicines; Financial Interests, Personal, Research Grant, Grant/Contract: Verastem; Financial Interests, Personal, Advisory Role, Consulting: AbbVie; Financial Interests, Personal, Advisory Role, Consulting: Adicet; Financial Interests, Personal, Advisory Role, Consulting: Amgen; Financial Interests, Personal, Advisory Role, Consulting: Ariad; Financial Interests, Personal, Advisory Role, Consulting: Bayer; Financial Interests, Personal, Advisory Role, Consulting: Clovis Oncology; Financial Interests, Personal, Advisory Role, Consulting: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting: Celgene; Financial Interests, Personal, Advisory Role, Consulting: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting: Instil Bio; Financial Interests, Personal, Advisory Role, Consulting: Genentech; Financial Interests, Personal, Advisory Role, Consulting: Gilead; Financial Interests, Personal, Advisory Role, Consulting: Lilly; Financial Interests, Personal, Advisory Role, Consulting: Janssen; Financial Interests, Personal, Advisory Role, Consulting: MedImmune; Financial Interests, Personal, Advisory Role, Consulting: Merck; Financial Interests, Personal, Advisory Role, Consulting: Novartis; Financial Interests, Personal, Advisory Role, Consulting: Roche; Financial Interests, Personal, Advisory Role, Consulting: Tyme Oncology; Financial Interests, Personal, Advisory Role, Consulting: Xcovery; Financial Interests, Personal, Advisory Role, Consulting: Virogin Biotech; Financial Interests, Personal, Advisory Role, Consulting: Maverick Therapeutics; Financial Interests, Personal, Other, Data safety board/Advisory board: Virogin Biotech; Financial Interests, Personal, Other, Data safety board/Advisory board: Maverick therapeutics; Financial Interests, Personal, Stocks/Shares: Virogin Biotech; Non-Financial Interests, Personal, Other, Immediate family member employed: Johnson & Johnson / Janssen. I. Melero: Financial Interests, Institutional, Sponsor/Funding: Immunocore. F. Thistlethwaite: Financial Interests, Personal, Advisory Board, Ad board: Achilles; Financial Interests, Personal, Advisory Board: Adicet; Financial Interests, Personal, Advisory Board, Honoraria: Bayer; Financial Interests, Personal, Advisory Board, Ad board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Ad board: Evelo Therapeutics; Financial Interests, Personal, Advisory Board, Ad boards: GSK; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board, Adboard/consultancy: Tknife; Financial Interests, Personal, Advisory Board, Ad board: Zelluna; Financial Interests, Institutional, Other, iMATCH is a 12 partner consortium funded by not for profit Innovate UK : IMATCH; Financial Interests, Institutional, Officer, Clinical lead for this 10 partner consortium of clinical academic and commercial partners: SAMPLE; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Principal Investigator: Achilles Ltd; Financial Interests, Institutional, Principal Investigator: Adaptimmune; Financial Interests, Institutional, Principal Investigator: Agalimmune Ltd; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Aveo; Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: Chugai; Financial Interests, Institutional, Principal Investigator: CytomX; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: GenMab; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: Immunocore; Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Institutional, Principal Investigator: Kymab Ltd; Financial Interests, Institutional, Principal Investigator: Millenium Pharmaceuticals/Takeda; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: Synthon; Other, Personal, Other, Panel member for a funding committee (MRC is a UK government NFP organisation): MRC DPFS panel member. K.N. Moore: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Aravive; Financial Interests, Personal, Advisory Board: Alkemeres; Financial Interests, Personal, Advisory Board: Blueprint; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Elevar; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: GSK/Tesaro; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: IMab; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Myriad; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Mereo; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: VBL Therapeutics; Financial Interests, Institutional, Research Grant: PTC Therapeutcs; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: GSK/Tesaro. N.H. Segal: Financial Interests, Personal, Advisory Role, Consulting/ advisory board: Immunocore; Financial Interests, Personal, Advisory Role, Consulting/ advisory board: PsiOxus; Financial Interests, Personal, Advisory Role, Consulting/ advisory board: Roche/Genentech; Financial Interests, Personal, Advisory Role, Consulting/ advisory board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role, Consulting/ advisory board: Revitope; Financial Interests, Personal, Advisory Role, Consulting/ advisory board: ABL Bio; Financial Interests, Personal, Advisory Role, Consulting/ advisory board: Novartis; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Immunocore; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche/Genentech. E. Garralda: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Thermo Fisher; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: BeiGene; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: F.Hoffmann/La Roche; Financial Interests, Personal, Advisory Role: Ellipses Pharma; Financial Interests, Personal, Advisory Role: Neomed Therapeutics1 Inc; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Janssen Global Services; Financial Interests, Personal, Advisory Role: SeaGen; Financial Interests, Personal, Advisory Role: TFS; Financial Interests, Personal, Advisory Role: Alkermes; Financial Interests, Personal, Advisory Role: Thermo Fisher; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: MabDiscovery; Financial Interests, Personal, Advisory Role: Anaveon; Financial Interests, Personal, Other, Travel Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel Grant: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel Grant: Menarini; Financial Interests, Personal, Other, Travel Grant: Glycotope; Financial Interests, Personal, Speaker's Bureau: Merck Sharp & Dohme; Financial Interests, Personal, Speaker's Bureau: Roche; Financial Interests, Personal, Speaker's Bureau: Thermo Fisher; Financial Interests, Personal, Speaker's Bureau: Lilly; Financial Interests, Institutional, Principal Investigator: Affimed Gmbh; Financial Interests, Institutional, Principal Investigator: Amgen SA; Financial Interests, Institutional, Principal Investigator: Anaveon AG; Financial Interests, Institutional, Principal Investigator: AstraZeneca AB; Financial Interests, Institutional, Principal Investigator: Biontech Gmbh; Financial Interests, Institutional, Principal Investigator: Catalym Gmbh; Financial Interests, Institutional, Principal Investigator: Cytomx; Financial Interests, Institutional, Principal Investigator: F.Hoffmann La Roche Ltd; Financial Interests, Institutional, Principal Investigator: F-Star Beta Limited; Financial Interests, Institutional, Principal Investigator: Genentech Inc; Financial Interests, Institutional, Principal Investigator: Genmab B.V.; Financial Interests, Institutional, Principal Investigator: Hutchison Medipharma Limited; Financial Interests, Institutional, Principal Investigator: Icon; Financial Interests, Institutional, Principal Investigator: Imcheck Therapeutics; Financial Interests, Institutional, Principal Investigator: Immunocore Ltd; Financial Interests, Institutional, Principal Investigator: Janssen-Cilag SA; Financial Interests, Institutional, Principal Investigator: Medimmune Llc; Financial Interests, Institutional, Principal Investigator: Merck Kgga; Financial Interests, Institutional, Principal Investigator: Novartis Farmacéutica, S.A; Financial Interests, Institutional, Principal Investigator: Peptomyc; Financial Interests, Institutional, Principal Investigator: Ribon Therapeutics; Financial Interests, Institutional, Principal Investigator: Roche Farma SA; Financial Interests, Institutional, Principal Investigator: Seattle Genetics Inc; Financial Interests, Institutional, Principal Investigator: Symphogen A/S; Financial Interests, Institutional, Principal Investigator: Taiho Pharma Usa Inc. B. Wilky: Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Springworks; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Adaptimmune; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Epizyme; Financial Interests, Personal, Advisory Role: Adcendo; Financial Interests, Personal, Research Grant: Agenus; Financial Interests, Personal, Research Grant: Exelixis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Deciphera; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Adaptimmune; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo. H. Arkenau: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bicycle; Financial Interests, Personal, Advisory Role: Bicycle; Financial Interests, Personal, Advisory Role: Engitix; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Role: ONC; Financial Interests, Personal, Advisory Role: Lab genius; Financial Interests, Personal, Advisory Role: Cell centric; Financial Interests, Personal, Advisory Role: Beigene; Financial Interests, Personal, Advisory Board: Taiko; Financial Interests, Personal, Full or part-time Employment: Sarah Cannon; Financial Interests, Institutional, Full or part-time Employment: Sarah Cannon. T.R. J. Evans: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Personal, Other, Support to attend international conferences: Bayer; Financial Interests, Institutional, Advisory Board: Bicycle Therapeutics; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Other, Support to attend international conferences: Bristol Myers Squibb; Financial Interests, Personal, Other, Support to attend international conferences: Celgene; Financial Interests, Institutional, Advisory Board: Clovis; Financial Interests, Institutional, Advisory Board: Eisai; Financial Interests, Institutional, Invited Speaker: Eisai; Financial Interests, Institutional, Advisory Board: Medivir; 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Non-Financial Interests, Personal, Other, Member of Clinical Experts Review Panel / Clinical Research Committee: Cancer Research; 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, Cancer Society Member: America Association for Cancer Research; Non-Financial Interests, Personal, Member, Cancer Society Member: American Society of Clinical Oncology; Non-Financial Interests, Personal, Member, Cancer Society Member: Association of Cancer Physicians (UK); Non-Financial Interests, Personal, Member, Cancer Society Member: British Association for Cancer Research; Non-Financial Interests, Personal, Member, Cancer Society Member: European Association for Cancer Research; Non-Financial Interests, Personal, Member, Cancer Society Member: International Liver Cancer Association; Other, Personal, Other, Clinical Subjects Editor: British Journal of Cancer; Other, Personal, Other, Chair of Independent Data Monitoring Committee P1trial: Genmab. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Acerta; Financial Interests, Institutional, Research Grant: Adaptimmune; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Apexigen; Financial Interests, Institutional, Research Grant: Arcus Biosciences; Financial Interests, Institutional, Research Grant: Array BioPharma; Financial Interests, Institutional, Research Grant: Artios Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Atreca; Financial Interests, Institutional, Research Grant: BeiGene; Financial Interests, Institutional, Research Grant: BerGenBio; Financial Interests, Institutional, Research Grant: BioAtla; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Calithera Biosciences; Financial Interests, Institutional, Research Grant: Checkpoint Therapeutics; Financial Interests, Institutional, Research Grant: Corvus Pharmaceuticals; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: CytomX; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Dracen Pharmaceuticals; Financial Interests, Institutional, Research Grant: Dynavax; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Elicio Therapeutics; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Erasca; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: Genocea Biosciences; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Gritstone Oncology; Financial Interests, Institutional, Research Grant: Guardant Health; Financial Interests, Institutional, Research Grant: Harpoon; Financial Interests, Institutional, Research Grant: Helsinn Healthcare SA; Financial Interests, Institutional, Research Grant: Hengrui Therapeutics; Financial Interests, Institutional, Research Grant: Hutchison MediPharma; Financial Interests, Institutional, Research Grant: IDEAYA Biosciences; Financial Interests, Institutional, Research Grant: IGM Biosciences; Financial Interests, Institutional, Research Grant: Immunocore; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Jounce Therapeutics; Financial Interests, Institutional, Research Grant: Kadmon Pharmaceuticals; Financial Interests, Institutional, Research Grant: Loxo Oncology; Financial Interests, Institutional, Research Grant: Lycera; Financial Interests, Institutional, Research Grant: Memorial Sloan-Kettering; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Mirati Therapeutics; Financial Interests, Institutional, Research Grant: NeoImmune Tech; Financial Interests, Institutional, Research Grant: Neovia Oncology; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Numab Therapeutics; Financial Interests, Institutional, Research Grant: OncoMed Pharmaceuticals; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: PMV Pharmaceuticals; Financial Interests, Institutional, Research Grant: RasCal Therapeutics; Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals; Financial Interests, Institutional, Research Grant: Relay Therapeutics; Financial Interests, Institutional, Research Grant: Revolution Medicines; Financial Interests, Institutional, Research Grant: Ribon Therapeutics; Financial Interests, Institutional, Research Grant: Rubius Therapeutics; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Seven and Eight Biopharmaceuticals / Birdie Biopharmaceuticals; Financial Interests, Institutional, Research Grant: Shattuck Labs; Financial Interests, Institutional, Research Grant: Silicon Therapeutics; Financial Interests, Institutional, Research Grant: Stem CentRx; Financial Interests, Institutional, Research Grant: Syndax Pharmaceuticals; Financial Interests, Institutional, Research Grant: Takeda Pharmaceuticals; Financial Interests, Institutional, Research Grant: Tarveda; Financial Interests, Institutional, Research Grant: TCR2 Therapeutics; Financial Interests, Institutional, Research Grant: Tempest Therapeutics; Financial Interests, Institutional, Research Grant: Tizona Therapeutics; Financial Interests, Institutional, Research Grant: TMUNITY Therapeutics; Financial Interests, Institutional, Research Grant: Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: University of Michigan; Financial Interests, Institutional, Research Grant: Vyriad; Financial Interests, Institutional, Research Grant: WindMIL; Financial Interests, Institutional, Research Grant: Y-mAbs Therapeutics; Financial Interests, Institutional, Advisory Role: AbbVie; Financial Interests, Institutional, Advisory Role: Achilles Therapeutics; Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Axelia Oncology; Financial Interests, Institutional, Advisory Role: Atreca; Financial Interests, Institutional, Advisory Role: Black Diamond; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role: Calithera Biosciences; Financial Interests, Institutional, Advisory Role: Checkpoint Therapeutics; Financial Interests, Institutional, Advisory Role: CytomX Therapeutics; Financial Interests, Institutional, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role: EcoR1; Financial Interests, Institutional, Advisory Role: Editas Medicine; Financial Interests, Institutional, Advisory Role: Eisai; Financial Interests, Institutional, Advisory Role: EMD Serono; Financial Interests, Institutional, Advisory Role: G1 Therapeutics; Financial Interests, Institutional, Advisory Role: Genentech / Roche; Financial Interests, Institutional, Advisory Role: Genmab; Financial Interests, Institutional, Advisory Role: GlaxoSmithKline; Financial Interests, Institutional, : Gritstone Oncology. M. Dar: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. C. Holland: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. S. Marshall: 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. P. Kirk: 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; Financial Interests, Institutional, Research Grant: Basilea; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Personal, Advisory Board: Basilea; Financial Interests, Personal, Advisory Board: Ellipses. All other authors have declared no conflicts of interest. BackgroundTCR bispecific proteins (bsp) redirect polyclonal T cells to target intra/extracellular proteins in cancer, as validated by tebentafusp (CD3×gp100 TCR) with a survival benefit in metastatic uveal melanoma (HR 0.51). IMC-C103C is a TCR bsp against MAGE-A4, a cancer-testis antigen expressed in several tumor types (eg, lung, ovarian, HNSCC, GEJ) but minimally in normal tissue. TCR bispecific proteins (bsp) redirect polyclonal T cells to target intra/extracellular proteins in cancer, as validated by tebentafusp (CD3×gp100 TCR) with a survival benefit in metastatic uveal melanoma (HR 0.51). IMC-C103C is a TCR bsp against MAGE-A4, a cancer-testis antigen expressed in several tumor types (eg, lung, ovarian, HNSCC, GEJ) but minimally in normal tissue. MethodsHLA-A*02:01+ pts with selected advanced tumors are eligible; prospective MAGE-A4 testing is required in indications with lower MAGE-A4 prevalence. The Ph1 primary objective is to identify the expansion dose. Other objectives: adverse events (AE), clinical activity (RECIST v1.1), biomarkers. IMC-C103C is dosed IV weekly, with step-dosing at > 15 μg (full dose at Day 15). HLA-A*02:01+ pts with selected advanced tumors are eligible; prospective MAGE-A4 testing is required in indications with lower MAGE-A4 prevalence. The Ph1 primary objective is to identify the expansion dose. Other objectives: adverse events (AE), clinical activity (RECIST v1.1), biomarkers. IMC-C103C is dosed IV weekly, with step-dosing at > 15 μg (full dose at Day 15). ResultsTable: 91PImmune cell activation markers, day 15-16Day 15 Dose, μgN treated*Blood lymphocytes % decrease, medianSerum IL6 fold increase, medianDetectable IFNg (>LLOD) n/N0.5-4.57Not done1.20/715-6420-605.32/18903-78281/31406-89344/62404-93504/4*40/42 pts treated on Day 15; only 13/18 pts received ≥ 90 μg dose on day 15. Open table in a new tab *40/42 pts treated on Day 15; only 13/18 pts received ≥ 90 μg dose on day 15. ConclusionsIMC-C103C is tolerable, demonstrates pharmacodynamic activity consistent with T cell activation (initially at ≥ 15 μg, consistently and robustly at ≥ 90 μg), drives T cells into tumor, and is clinically active. Dose optimization is ongoing. IMC-C103C is tolerable, demonstrates pharmacodynamic activity consistent with T cell activation (initially at ≥ 15 μg, consistently and robustly at ≥ 90 μg), drives T cells into tumor, and is clinically active. Dose optimization is ongoing.
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