On April 9, 2024 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies ("ETBs"), to create novel therapies with potent differentiated mechanisms of action for cancer, reported 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 (AACR) (Free AACR Whitepaper) Annual Meeting taking place in San Diego, CA, and also announced monotherapy response activity in Head and Neck Cancer (Press release, Molecular Templates, APR 9, 2024, View Source [SID1234641948]).

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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.
"We are excited to see objective responses in heavily pre-treated, checkpoint-experienced, head and neck cancer patients, a setting with high unmet medical need," said CEO Eric Poma. "The long-lasting partial responses were in patients with low PD-L1 expression and showed concomitant increases in cytokines associated with T-cell activation and tumor microenvironment remodeling not seen with other checkpoint therapies. We believe the novel mechanism of action of MT-6402 may allow for durable, T-cell-mediated, monotherapy activity in patients who have progressed on checkpoint therapy. Based on the preliminary signals of single agent activity with MT-6402, an expansion study in low PD-L1 head and neck cancer patients to further evaluate MT-6402 has been initiated."

AACR Presentation
Title: 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
Location: Section 48, Poster #19, Abstract #CT191
Date/Time: 9am – 12:30pm PT Tuesday, April 9, 2024
The abstract will be available in the Presentations section of MTEM’s website.