ArticleJournal for immunotherapy of cancer2025
TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 8 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I, First-in-Human, Open-Label, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of M6223, an Inhibitor of TIGIT, as Single Agent and in Combination With Bintrafusp Alfa (Anti-PDL1/ TGFß Trap) in Participants With Metastatic or Locally Advanced Solid Unresectable Tumors
A Phase II, Multicenter, Randomized, Open Label, Parallel-Arm, Umbrella Study of Avelumab (MSB0010718C) in Combination With Other AntiTumor Agents as a Maintenance Treatment in Participants With Locally Advanced or Metastatic Urothelial Carcinoma Whose Disease Did Not Progress With First Line Platinum-Containing Chemotherapy (JAVELIN Bladder Medley)
Who cites it
8 citing papers in PubMed.
- The Right Key, the Wrong Lock: TIGIT Checkpoint Blockade and the Road to Precision Immunotherapy.Pharmaceutics · 2026Review
- Radiation-Induced Alterations in Cancer-Associated Fibroblasts: Drivers of Tumor Radioresistance and Therapeutic Targets.Biomolecules · 2026Review
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Immunotherapy in Asia: current insights and prospects in Southeast Asia and Malaysia.Frontiers in oncology · 2026Review
- Model-Informed Selection of the Recommended Phase 2 Dosage for Anti-TIGIT Immunotherapy Leveraging co-Expressed PD-1 Inhibitor Target Engagement.Clinical pharmacology and therapeutics · 2025Article
- Exploring NUP62's role in cancer progression, tumor immunity, and treatment response: insights from multi-omics analysis.Frontiers in immunology · 2025Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundM6223 is an intravenous (IV), Fc-competent, fully human, antagonistic, anti-T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibody. Bintrafusp alfa (BA) is a bifunctional fusion protein that simultaneously blocks nonredundant immunosuppressive TGF-β and PD-(L)1 pathways.
methodsThis first-in-human, dose-escalation study in patients with advanced solid tumors (N=58; aged ≥18 years, ECOG PS≤1) evaluated M6223 alone (Part 1A, n=40; M6223 10-2400 mg every 2 weeks, n=32; M6223 2400 mg every 3 weeks, n=8) or with BA (Part 1B, n=18; M6223 300-1600 mg with BA 1200 mg; both every 2 weeks, intravenous). Primary objectives were safety, tolerability, maximum tolerated dose (MTD) and recommended dose for expansion (RDE). Additional objectives included pharmacokinetics, pharmacodynamics and clinical activity (NCT04457778).
resultsTwo dose-limiting toxicities were observed: grade 3 adrenal insufficiency (Part 1A: M6223 900 mg every 2 weeks) and grade 3 anemia (Part 1B: M6223 300 mg, only BA related). MTD was not reached. Overall, median overall survival and progression-free survival were 7.6 (95% CI 4.9, 12.0) and 1.4 (95% CI 1.3, 1.8) months, respectively. Stable disease as best response was observed in 13 (32.5%) and 5 (27.8%) patients in parts 1A and 1B, respectively. M6223±BA displayed a linear pharmacokinetic profile. Anti-TIGIT mode-of-action-related pharmacodynamic effects were observed in peripheral blood and in tumor tissue. RDEs were 1600 mg every 2 weeks or 2400 mg every 3 weeks for M6223 monotherapy and 1600+1200 mg every 2 weeks for M6223+BA.
conclusionsM6223±BA had a manageable safety profile, with RDEs defined for both monotherapy and combination therapy. Further evaluation of M6223 is ongoing in combination with the PD-L1 inhibitor avelumab in patients with advanced urothelial carcinoma (JAVELIN Bladder Medley; NCT05327530). TRIAL REGISTRATION NUMBER: NCT04457778.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.