Dr Spira on the Ongoing Investigation of MYTX-011 in NSCLC

Alexander I. Spira, MD, PhD, FACP, co-director, Virginia Cancer Specialists Research Institute, director, Thoracic and Phase I Program, clinical assistant professor, Johns Hopkins School of Medicine, discusses a phase 1 study (NCT05652868) of the antibody-drug conjugate (ADC) MYTX-011 in patients with non–small cell lung cancer (NSCLC).

MYTX-011 is an ADC consisting of a vcMMAE linker-payload conjugated to a novel, pH-dependent, anti-cMET IgG1 antibody, Spira begins. cMET expression is often upregulated in NSCLC, and has been identified as a resistance mechanism for several approved EGFR-targeted kinase inhibitors. MYTX-011 was engineered to increase on-target uptake in cMET-expressing tumors, Spira states. In preclinical studies, the agent displayed increased tumor internalization and cytotoxicity vs a surrogate of an advanced clinical stage cMET ADC. The drug's unique mechanism of action, early efficacy, favorable pharmacokinetics, and comparable toxicity profile indicate its potential value as a therapeutic alternative for patients with refractory tumors, Spira explains. Notably, t may provide benefit across multiple tumor types, including NSCLC, he adds.

A first-in-human, phase 1 dose escalation and dose expansion study was designed to evaluate the preliminary antitumor activity and safety of MYTX-011 in patients with NSCLC who have varying degrees of cMET positivity, Spira details. The dose-escalation phase will enroll patients with previously treated, locally advanced or metastatic NSCLC who are unselected for cMET expression. Patients will receive 1of 6 dose levels of intravenous MTYX-011. The recommended phase 2 dose of MTYx-011 will then be determined by the safety, tolerability, pharmacokinetics, and initial activity of MYTX-011.

The dose-expansion portion of the study will begin once the recommended phase 2 dose has been determined. This portion of the study will enroll patients with NSCLC and no actionable EGFR mutations into 1 of 5 different cohorts based on cMET IHC positivity or MET amplification.

The phase 1 portion of the trial is currently ongoing and enrolling patients, Spira concludes.