MT-6402 Lands FDA Fast Track Designation for PD-L1+ Non–Small Cell Lung Cancer

The FDA has granted fast track designation to MT-6402 for the treatment of patients with advanced non–small cell lung cancer (NSCLC) expressing PD-1, according to a press release issued by Molecular Templates, Inc.¹

MT-6402 is a de-immunized engineered toxin body that targets PD-1 in solid tumors that carry Shiga-like Toxin A payload. The agent had added cytomegalovirus antigen seeding technology that allows it to internalize the PD-L1 receptor bound to the agent. According to preclinical research, MT-6402 promotes tumor cell death, reduces tumor volume, and redirects CMV-specific T-cell responses.

“Fast track designation is an acknowledgment from the FDA of the potential of MT-6402 to address a significant unmet need in NSCLC,” said Roger Waltzman, chief medical officer, Molecular Therapeutics, in the release. “This designation will allow for continued contact with the FDA regarding the ongoing clinical program as well as future studies.”

A first-in-human, open-label, dose-escalation, and dose-expansion study of MT-6402 for the treatment of patients with PD-L1 expressing advanced solid tumors was recently initiated (NCT04795713).^2,3

The study will be conducted in 2 sequential parts. Part 1 will be the dose-escalation portion of the study during which investigators will evaluate the safety and tolerability of Mt-6402 as well as determine the maximum-tolerated dose of the agent. In part 2, the dose-expansion portion of the study, the primary end points will include finding the recommended phase 2 dose of MT-6402 and efficacy defined by objective response rate per RECIST v1.1. The secondary end points of the study include pharmacokinetics, ORR per RECIST v1.1 in patients with advanced cancer, duration of response, progression-free survival, overall survival, and the immunogenicity of MT-6402 determined by the number of anti-drug antibodies.³

To be eligible for part 1, patients must be aged 18 years or older with a histologically confirmed, unresectable, locally advanced, or metastatic PD-L1 expressing solid tumor. PD-L1 expression must have been detected on an FDA-approved immunohistochemistry assay using the most recent tissue available for the patient. Patients are also required to have measurable disease.

For inclusion in part 2 of the study, patients are required to be 18 years of age or older with histologically confirmed, unresectable, locally advanced, or metastatic PD-L1 expressing solid tumor that cannot be treated with standard-of-care therapy. Patients in part 2 are also required to have an ECOG performance status of 0 or 1, prior treatment with a checkpoint inhibitor, adequate bone marrow function, adequate hepatic function, and adequate serum albumin. The part 2 cohort will include patients with NSCLC, as well as those with head and neck squamous cell carcinoma, and skin squamous cell carcinoma.

Patients who meet the inclusion criteria are actively being recruited at centers in California, Georgia, Illinois, Missouri, North Carolina, Pennsylvania, Tennessee, and Texas.

With a fast track designation, the development of MT-6402 will be accelerated and applications to the FDA for the drug will undergo quick reviews. Fast track designations are designed to help fill unmet medical needs.¹

_References:

_{1. Molecular Templates, Inc. announces fast track designation granted by FDA for MT-6402. News release. November 18, 2021. Accessed November 18, 2021. https://bit.ly/2YY76O0}

_{2. Spigel DR, Anand B, Carroll B, et al. P47.13 First-in-Human, Dose escalation and expansion study of MT-6402 in patients with pd-l1 expressing advanced solid tumors. J Thorac Oncol. 2021; 16(10);S1102. doi: 10.1016/j.jtho.2021.08.506}

_{3. Study of MT-6402 in subjects with advanced solid cancer that expresses PD-L1. Clinicaltrials.gov. Accessed November 18, 2021. https://bit.ly/3l9WUdp}