680TiP - A phase I/IIa first-in-human clinical trial evaluating MDX2001, a multi-specific antibody in patients with advanced solid tumor malignancies

Background

MDX2001 is a tetraspecific T cell engager antibody recognizing CD3 and CD28 on human T cells, and c-MET and TROP2 on certain tumors. Anti-CD3 provides the primary signal for T cell activation while anti-CD28 delivers the secondary signal for enhanced T cell activation, survival and proliferation. Combinatorial targeting of c-MET and TROP2 by MDX2001, either on the same or different cancer cells, is hypothesized to provide more effective engagement of tumor cells by T cells and may better address tumor heterogenicity and treatment escape/resistance.

Trial design

This Phase 1/2a multicenter, open-label clinical trial explores MDX2001 in patients with selected advanced solid tumor malignancies. The study design consists of Phase 1a dose escalation guided by a Bayesian Optimal Interval design with a target maximum tolerated dose toxicity rate of 30%, a Phase 1b dose expansion in a single indication, and Phase 2a recommended Phase 2 dose (RP2D) expansion in a single indication. Patients with selected tumors known to have high rates of TROP2 or c-MET expression are eligible for Phase 1a where escalating doses of MDX2001 are given intravenously in sequential escalation cohorts. In a single Phase 1b indication, patients will be randomized 1:1 into 2 dose cohorts using a Bayesian Optimal Phase 2 (BOP2) design. Once a RP2D is determined, Phase 2a will enroll approximately 30 patients into a single cohort using a BOP2 design. The primary objectives of this study are to characterize the safety, tolerability, and anti-tumor activity of MDX2001 in patients with advanced solid tumors. Secondary objectives include characterizing MDX2001 pharmacokinetics, immunogenicity, and evaluating the relationship between baseline tumor target protein expression and clinical benefit. Patients will have radiographic tumor assessments every 8 weeks and will continue to receive treatment until disease progression per RECIST v1.1 (as assessed by the investigator), unacceptable toxicity, withdrawal of consent or the sponsor terminates the study, whichever occurs first. The study will be conducted in United States,United Kingdom, Europe, and Asia.

Clinical trial identification

NCT06239194.

Editorial acknowledgement

Legal entity responsible for the study

ModeX Therapeutics, an OPKO Health Company.

Funding

ModeX Therapeutics, an OPKO Health Company.

Disclosure

A.R. Minchom: Financial Interests, Personal, Other, Expenses: Amgen Pharmaceuticals, Loxo oncology; Financial Interests, Personal, Invited Speaker: Bayer Pharmaceuticals, Chugai Pharmaceuticls, GSK, Janssen Pharmaceuticals, Merck Pharmaceuticals; Financial Interests, Personal, Advisory Board: Faron Pharmaceuticals, GSK, Janssen Pharmaceuticals, Merck Pharmaceuticals, Takeda, Genmab; Financial Interests, Institutional, Other, Research funding: MSD, Merck Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Novartis Oncology. K. Culm: Financial Interests, Personal, Stocks or ownership: BMS; Financial Interests, Personal, Full or part-time Employment: ModeX Therapeutics. E. Garmey: Financial Interests, Personal, Other, Paid medical consultant: Grifols, Aldeyra, Bicycle Therapeutics, Circle Pharma, Finch Therapeutics, Genocea Biosciences, Genzada, Gigagen, H3 BioScience, HiFi Bio, ImmuneSensor Therapeutics, ImmunoMet, Linnaeus Therapeutics, ModeX Therapeutics, NED BioSystems, Novita Pharma, OncoHeroes, Raze Therapeutics, Sensei Therapeutics, Shasqi, Tagworks, Targimmune, Tarveda, X4 Therapeutics; Non-Financial Interests, Member of Board of Directors: Beth Israel Deaconess Hospital. L. Makris: Financial Interests, Personal, Speaker, Consultant, Advisor: ModeX Therapeutics, Various. M.L. Johnson: Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arcus Biosciences, Arrivent, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Immunocore, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Pyramid Biosciences, Alentis Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, D3 Bio Limitied, Fate Therapeutics, Gilead Sciences, Hookipa Biotech, Lilly, Normunity, Novocure, Pfizer, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, VBL Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Adaptimmune, Amgen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, Ideaya Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Kartos Therapeutics, Loxo Oncology, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight BioPharmaceuticals/Birdie BioPharmaceuticals, Shattuck Labs, Silicon Therapeutics, Syndax Pharmaceuticals, Takeda Pharmaceuticals, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, Turning Point Therapeutics, Vyriad, Y-mAbs Therapeutics, ArriVent BioPharma, Bayer, LockBody Therapeutics, Taiho Oncology, Conjupro, Immuneering Corporation, Impact Therapeutics, NextPoint Therapeutics, OncoC4, Summit Therapeutics, Systimmune, TheRas, Vividion. D. Sommerhalder: Financial Interests, Personal, Other, Ad-hoc advisory role: Syneos SAG; Financial Interests, Personal, Other, Medical consulting: Guidepoint; Financial Interests, Institutional, Full or part-time Employment, Employed as a physician by Texas Oncology, a for-profit entity.: Texas Oncology/US Oncology; Financial Interests, Personal, Stocks/Shares, Shareholder: NEXT Oncology, Texas Oncology; Financial Interests, Institutional, Local PI: AbbVie, Astellas, BJ Biosciences, BioNTech, Biomea Fusion, Boehringer Ingelheim, Bristol Myers Squibb, Fate Therapeutics, Gilead Sciences, Iconovir Bio, Immuneering, Kura Oncology, MediLink Therapeutics, Mirati Therapeutics, Monopteros Therapeutics, NGM BioPharmaceuticals, Navire, Nimbus Saturn, OncoResponse Inc, Parthenon, Pfizer, Revolution Medicines, Symphogen, Tachyon Therapeutics, Teon Therapeutics, Tyligand Bioscience, Vividion Therapeutics, ZielBio. E. Garralda: Financial Interests, Personal, Invited Speaker: MSD, Roche, Thermo Fisher, Novartis, SeaGen; Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte, Medscape; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. J. Henry: Financial Interests, Personal, Principal Investigator: Various. M. Yang, D. Burzyn, V. Chhaljani: Financial Interests, Personal, Full or part-time Employment: ModeX Therapeutics. M.M. Cotreau: Financial Interests, Personal, Advisory Role: ModeX Therapeutics; Financial Interests, Personal, Stocks/Shares: Abcuro, Alnylam, ImmunoGen. A. Goenaga: Financial Interests, Personal, Full or part-time Employment: ModeX Therapeutics; Financial Interests, Personal, Stocks/Shares: Pfizer. Z. Yang: Financial Interests, Personal, Full or part-time Employment: ModeX Therapeutics; Financial Interests, Personal, Stocks/Shares: OPKO Health. R. Wei: Financial Interests, Personal, Full or part-time Employment: ModeX Therapeutics; Financial Interests, Personal, Stocks/Shares: Sanofi, OPKO Health. J. Mascola: Financial Interests, Personal, Leadership Role: ModeX Therapeutics. G. Nabel: Financial Interests, Personal, Leadership Role: ModeX Therapeutics, Siga Technologiest, Candel Therapeutics; Financial Interests, Personal, Advisory Role: OKPO Health; Financial Interests, Personal, Stocks/Shares: Moderna, Medtronic, Lyell Immunopharma, Accolade Hospice. E.E. Dumbrava: Financial Interests, Institutional, Other, Research/grant funding: Bayer HealthCare Pharmaceuticals, Immunocore Ltd, Amgen, Aileron Therapeutics, Compugen Ltd, Gilead, BOLT Therapeutics, Aprea Therapeutics, Bellicum, PMV Pharma, Triumvira, Seagen Inc, Mereo BioPharma 5 Inc, Sanofi, Rain Oncology, Astex Therapeutics, Sotio, Mersana Therapeutics, Poseida, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: PMV Pharma; Financial Interests, Personal, Advisory Board: BOLT Therapeutics, Mersana Therapeutics, Orum Therapeutics, Summit Therapeutics. All other authors have declared no conflicts of interest.