Molecular Templates, Inc. announced that MTEM will present a poster, "First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data," at the 2024 American Association for Cancer Research Annual Meeting taking place in San Diego, CA, and also announced monotherapy response activity in Head and Neck Cancer. The poster highlighted the following findings from the phase I dose-escalation study of MT-6402: MT-6402 has been well tolerated with no drug-related Grade 4 or Grade 5 adverse events observed; MT-6402 acts uniquely from other approved checkpoint agents. MT-6402 depletes immunosuppressive PD-L1+ immune cells and tumor cells, activates a T-effector phenotype, and remodels the tumor microenvironment to restore T-cell surveillance of the tumor.

An early monotherapy efficacy signal in head and neck squamous cell carcinoma (HNSCC) was identified. Nine patients with recurrent and metastatic heavily pre-treated and checkpoint-experienced HNSCC were treated in the phase I dose escalation of which two patients have confirmed durable PRs. 2 of the 9 patients with HNSCC treated with MT-6402 showed confirmed partial responses (one response was unconfirmed at the time of the poster?s submission but has subsequently been confirmed).

The patients remain on study at cycles 19 and 10, respectively (one cycle = 4 weeks), demonstrating the potential for durable monotherapy activity with MT-6402. Both patients had low PD-L1 tumor expression and had progressed after multiple lines of therapy including checkpoint. Additionally, both patients showed unique pharmacodynamic effects consistent with tumor microenvironment remodeling including reduction in myeloid derived suppressor cells (MDSCs) and modulation of VEGF.

Tumor reductions were observed in other patients including an unconfirmed PR.