On June 3, 2024 Mythic Therapeutics, a clinical-stage biotechnology company committed to the development of next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported initial dose escalation results from its ongoing Phase 1 KisMET-01 study evaluating its investigational cMET-targeting ADC, MYTX-011, in patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Mythic Therapeutics, JUN 3, 2024, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-presents-initial-dose-escalation-data-from-ongoing-phase-1-kismet-01-study-on-mytx-011-at-the-american-society-of-clinical-oncology-asco-annual-meeting [SID1234644019]).

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"The initial dose escalation results from our ongoing Phase 1 KisMET-01 study, coupled with the previously presented preclinical data are encouraging and underscore MYTX-011’s potential to serve patients with a broad range of cMET expression," said Gilles Gallant, BPharm, Ph.D., FOPQ, Chief Development Officer at Mythic Therapeutics. "ADCs have been a transformative class of treatment for patients impacted by cancer, but we know that there is a large population of patients with low-to-moderate target expression who are unlikely to benefit from them. These initial data potentially represent significant promise for patients who have historically been ineligible for treatment due to their level of target expression or tumor type, and we look forward to continuing our dose escalation and expansion study."

MYTX-011 is a novel cMET-targeted DAR 2 vcMMAE ADC with an antibody that has been engineered to have pH-dependent binding, which results in higher internalization and payload delivery to tumor cells with a range of cMET expression.

KisMET-01 (NCT05652868) is a multicenter, first-in-human study of MYTX-011 in patients with previously treated, locally advanced or metastatic NSCLC. The study is comprised of a Part 1 dose escalation in patients with NSCLC of any histology and regardless of cMET expression level, followed by Part 2 dose expansion in cohorts specified by cMET expression and histology. The primary objectives of Part 1 are to assess safety and tolerability and determine the recommended phase 2 dose. Secondary objectives include assessment of pharmacokinetics (PK) and preliminary anti-tumor activity.

As of April 30, 2024, 42 patients had been enrolled and received at least one dose of MYTX-011. Data from 41 patients was available by data cutoff and median follow-up was 15 weeks. Patients were dosed between 1.0 to 6.7 mg/kg on a once every three weeks schedule (Q3W). Treated patients had a median of three prior lines of therapy. As of data cutoff, PK data were available in patients who received doses 1.0 to 5.0 mg/kg. PK of MYTX-011 showed nearly dose proportional exposure up to 5.0 mg/kg. Little separation of ADC and total mAb concentration was noted, suggesting good stability of MYTX-011, supporting dosing every 3 weeks. MYTX-011 has been well tolerated with low incidence of common AEs associated with MMAE or cMET targeted therapeutics. No dose-limiting toxicity was reported, and dose escalation is ongoing. Given that dose escalation is ongoing and the overall median follow-up as of the data cutoff was 15 weeks, efficacy data will be presented in a future conference or publication.

"Patients with locally advanced or metastatic NSCLC who have not responded or become resistant to previous therapies represent an urgent unmet need," said Melissa Johnson, M.D., Director of Lung Cancer Research at Sarah Cannon Research Institute. "Observing the favorable safety, tolerability and PK of MYTX-011 across a diverse range of cMET-expressing patients is encouraging. We look forward to seeing additional safety and efficacy data from the Phase 1 study."

About MYTX-011

MYTX-011, an investigational cMET-targeting ADC, leverages Mythic’s innovative FateControl technology which is designed to allow ADCs to actively navigate inside of cells, potentially increasing delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).