During the annual meeting of the American Society of Clinical Oncology (ASCO) held June 2-6, 2023 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world will gather to discuss the latest research and how to ensure that all people receive the cancer care they need. Among the data to be presented is Mythic Therapeutics’ trial in progress on the company’s investigational cMET-targeting Antibody-drug Conjugates (ADC), MYTX-011 for the treatment of patients diagnosed with locally advanced, recurrent or metastatic Non-small cell lung cancer (NSCLC).
In NSCLC, expression of cMET is up-regulated by DNA amplification (2% to 5%), exon 14 skipping mutations (2% to 4%), and over-expression (30% to 60%). cMET up-regulation in NSCLC has also shown to be a resistance mechanism for several approved EGFR-targeted kinase inhibitors. As a result, it limits the effectiveness of these treatment options. Furthermore, while MET tyrosine kinase inhibitors have been approved and are commercially available, nearly 50% of all patients do not respond to these inhibitors, leading to inevitable resistance. [1]
A novel approach
MYTX-011 leverages Mythic’s innovative FateControl™ technology. This technology is designed to help ADCs to actively navigate inside of cells to potentially increase 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.
The poster presentation will highlight the trial design, dosing regimen and study protocol for the company’s ongoing Phase 1 KisMET-01 clinical trial evaluating the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of MYTX-011 in subjects with locally advanced, recurrent or metastatic NSCLC (NCT05652868).
“We’re looking forward to the presentation of this Trial in Progress poster and to the potential of our KisMET-01 Phase 1 clinical trial in NSCLC. This presentation follows the announcement of our first patient dosed earlier this year,” said Gilles Gallant, BPharm, PhD, FOPQ, Chief Development Officer at Mythic Therapeutics.
“By harnessing our novel FateControl™ technology, designed to improve ADC efficacy against a broad set of molecular targets and patient profiles, we aim to expand the use of ADCs to patients who have previously not been eligible for treatment due to their level of target expression or tumor type,” Gallant added.
High Unmet medical need
“There continues to be a high unmet need for patients with NSCLC as many either do not respond to, or develop resistance to, existing treatment options,” said presenting author and KisMET-01 study investigator Alexander Spira, MD, PhD, FACP, Next Oncology Virginia.
“Additionally, we’re excited to explore the potential for MYTX-011 in the Phase 1 KisMET-01 trial to provide a solution for the limitations of traditional ADCs, which have demonstrated potential efficacy as monotherapy only in patients whose tumors express high levels of cMET.”
Study design
The KisMET-01 Phase 1 clinical trial will be conducted in two parts—dose escalation and dose expansion—with patients receiving MYTX-011 intravenously every 21 days. Part 1 will assess the safety and tolerability of escalating doses of MYTX-011 as a single-agent in patients with advanced NSCLC to identify the recommended Phase 2 dose (RP2D). The dose escalation schedule is based on the Bayesian Optimal Interval (BOIN) design and doses may be escalated or de-escalated based on the BOIN algorithm. The recommended Phase 2 dose to be studied in Part 2 will be identified as a biologically active dose at or below the maximum tolerated dose.
The study’s Part 2 will include patients with NSCLC with cMET over-expression or MET amplification/exon 14 skipping mutations and will be initiated once the RP2D has been determined. Patients will be enrolled into different cohorts based on cMET over-expression and/or presence of MET genetic alterations and the safety, tolerability and preliminary anti-tumor activity of MYTX-011 will be assessed. cMET positivity thresholds for enrollment into the dose expansion cohorts were selected based on anti-tumor activity of MYTX-011 in preclinical models, published data for responses to cMET targeting agents and on the prevalence of cMET expression in clinical NSCLC samples.
Preclinical proof of concept data for MYTX-011 were recently presented at the 2023 annual meeting of the American Association for Cancer Research (AACR) 2023.[2]
Clinical trial
Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer – NCT05652868
Reference
[1] Spira AI, Johnson ML, Blumenschein GR, Burns TF, Thompson JR, Deshpande A, Comb WC, Fiske B, Gallant G, Heist RS. Phase 1 multicenter dose escalation and dose expansion study of antibody-drug conjugate (ADC) MYTX-011 in subjects with non-small cell lung cancer. J Clin Oncol 41, 2023 (suppl 16; abstr TPS9147)
[2] Gera N, Fitzgerald K, Ramesh V, Patel P, Kien L, Kanojia D, Aoyama S, Colombo F, Deshpande A, Comb W, Chittenden T, Fiske B. MYTX-011: A novel cMET-targeting antibody drug conjugate (ADC) engineered to increase on-target uptake in and efficacy against cMET expressing tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5000.
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