MYTX-011 in patients with previously treated locally advanced or metastatic NSCLC: Initial dose escalation results in the phase 1 KisMET-01 study.

8558 Background: MYTX-011 is a novel cMET-targeted vcMMAE antibody-drug conjugate with a humanized monoclonal 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. Initial dose escalation results from the ongoing KisMET-01 in patients (pts) with NSCLC are reported here. Methods: KisMET-01 (NCT05652868) is a multicenter, first-in-human study of MYTX-011 in pts with previously treated, locally advanced or metastatic NSCLC. The study is comprised of a dose escalation (Part 1) in patients with NSCLC of any histology and regardless of cMET expression level, followed by dose expansion (Part 2) in cohorts specified by cMET expression and histology. In Part 1, cMET expression by immunohistochemistry (IHC) is analyzed retrospectively whenever tumor tissue is available. 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. Results: As of 23 Jan 2024, 29 pts had enrolled and received ≥1 dose of MYTX-011 (dose range 1.0 to 5.0 mg/kg Q3W). Data from 27 pts was available by data cutoff (18 Jan 2024). Median follow-up time was 7 weeks (range, 3-26). Median age was 63 years (range, 28-80); pts had a median of 3 (range, 1-5) prior lines of therapy. 59% of the pts had non-squamous cell (non-SqCC) carcinoma, 26% had squamous cell carcinoma (SqCC), 4% had adenosquamous carcinoma, and histology type was not reported in 11% of the pts. 19% of the pts had MET amplification or MET exon 14 skipping mutation. Of the 11 pts with available cMET IHC results, 4 were classified as high (defined as ≥50% tumor cells at 3+ intensity) and 1 was classified as intermediate (≥25% and <50% tumor cells at 3+) cMET expression. No dose-limiting toxicities were reported. TEAEs ≥15% (any grade, grade ≥3) included corneal changes (30%, 0%), blurred vision (26%, 0%), fatigue (26%, 0%), dry eyes, (19%, 0%), and dyspnea (19%, 4%). Of the 6 pts (19%) who had grade ≥3 TEAEs, none were related to MYTX-011. Incidences of common AEs associated with MMAE or MET targeting, such as peripheral neuropathy, hematologic toxicities, elevated liver function tests, hypoalbuminemia, and peripheral edema, were absent or limited to grade 1 in <15% of pts. Preliminary anti-tumor activity was observed in non-SqCC and SqCC histology, and across cMET expression levels. Preliminary PK of MYTX-011 showed nearly dose proportional exposure and a half-life that supports dosing every 3 weeks. Conclusions: MYTX-011 has been well tolerated with low rates of common MMAE or MET targeted therapy-associated AEs. Preliminary anti-tumor activity and PK supports the development of MYTX-011 in a wide range of cMET-expressing NSCLC pts. Dose escalation is currently ongoing as of Feb 2024. Clinical trial information: NCT05652868 .