Abstract CT124: Interim results of a phase I clinical trial evaluating Fas ligand (FasL) blocking antibody M3T01 in adults with advanced treatment-refractory solid tumors

Abstract Background: FasL expressed on tumor endothelial cells, macrophages, and activated T cells contributes to apoptosis of tumor-specific T cells and impaired tumor infiltration by T cells. In preclinical models, blockade of FasL/Fas signaling results in enhanced T cell infiltration of tumors and augments the antitumor efficacy of immune checkpoint inhibitors and adoptive cell therapies. M3T01 is a fully human IgG4/kappa monoclonal anti-FasL blocking antibody. M3T01 is being evaluated in an ongoing first-in-human phase I clinical trial (NCT06719362). Methods: Dose escalation (3 + 3 design) of M3T01 as monotherapy (cohorts 1-5) and in combination with pembrolizumab (cohorts 6-8) is ongoing. Dose levels of M3T01 range from 100 to 800 mg intravenously every 3 weeks. Eligible patients have selected unresectable or metastatic solid tumors that have progressed through standard therapy. The primary objectives are to assess the safety/tolerability, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of M3T01. Secondary objectives include pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor efficacy of M3T01 as monotherapy and in combination with pembrolizumab. Results: As of the data cutoff, 10 patients (4 women, 6 men) with a median age of 68 have been treated across 3 dose escalation cohorts (100 mg, 200 mg, 400 mg). Treatment-related adverse events (TRAE) of any grade (CTCAE v5. 0) were reported in 5 of 10 patients (50%). Only one grade 3 TRAE was observed, immune thrombocytopenia (ITP), and there were no grade 4 or 5 TRAEs. The most common TRAEs included maculopapular rash (n=2, 20%), arthralgia (n=2, 20%), myalgia (n=1, 10%), chills (n=1, 10%), hypothyroidism (n=1, 10%), and ITP (n=1, 10%). No patients discontinued treatment due to TRAEs. No DLTs were observed and an MTD has not been reached. PK exposures increased approximately dose proportionally. Transient anti-drug antibodies (ADA) were observed without any impact on systemic exposure to M3T01. On-target pharmacodynamic potency of FasL inhibition was characterized, e. g. increased peripheral blood CD3+/CD4-/CD8- (double-negative) T cells. The best objective response observed with escalating doses of M3T01 monotherapy was stable disease in 6 of 10 patients (60%). Three patients demonstrated tumor regression including a patient with treatment refractory gastroesophageal (GEJ) adenocarcinoma in which several liver metastases decreased in size. Conclusion: Interim results of this first-in-human phase I clinical trial demonstrate that M3T01 has been well-tolerated and is showing approximately dose-proportional PK exposures. Preliminary signals of antitumor efficacy with M3T01 as monotherapy have been observed. These findings support the ongoing clinical development of this potent FasL inhibitor. Citation Format: Rom Leidner, Prakash Ambady, Emily M. Lin, Neda Jooya, Amber Ruiz, Cassandra Niemi, Christopher Darus, Binbin Zheng-Lin, Tara Foote, Ashley Drokin, Alexander T. Tran, Grayson DuRaine, Bernard Fox, Alan Korman, William L. Redmond, Matthew H. Taylor. Interim results of a phase I clinical trial evaluating Fas ligand (FasL) blocking antibody M3T01 in adults with advanced treatment-refractory solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT124.