MYTX-011, a cMET-targeting antibody-drug conjugate (ADC), in patients with previously treated, advanced NSCLC: Updated dose escalation results in the phase 1 KisMET-01 study.

• DOI: 10.1200/jco.2025.43.16_suppl.8613
• Publication Date: 2025-05-28T21:06:45Z
• Authors: Rebecca Heist; Elaine Shum; Ester Garcia; Malinda Itchins; Bo Gao; Ji-Youn Han; George R. Blumens...; Sarah Benafif; Mariam Alexander; Rohit Joshi; Jih-hsiang Lee; Nicholas Coupe; Nicolas Girard; Brian Fiske; Malina Traianova; William Tad Downing; Thao Nguyen; Ting-Hui Wu; Gilles Gallant; Hye Ryun Kim
• Keywords: Antibody-drug conjugate; Conjugate

8613 Background: MYTX-011 is a novel cMET-targeting vcMMAE ADC engineered for pH-dependent binding. This results in more efficient payload delivery, which drives efficacy tumors over wide range of cMET expression, including potentially >50% NSCLC patients (pts). Here we report safety and preliminary from dose escalation pts who received ≥4.0 mg/kg (mpk), the clinically active range, Phase 1 KisMET-01 study. Methods: (NCT05652868) multicenter, first-in-human study with previously treated, locally advanced or metastatic NSCLC. The comprises any histology followed by expansion cMET-positive (cMET+) selected immunohistochemistry (Ventana SP44). In escalation, expression analyzed whenever tumor tissue available. Results: As 7 Jan 2025, 85 ≥1 (1.0–8.3 mpk Q3W), 59 doses mpk. PK showed near proportional exposure low unconjugated MMAE across levels. mpk, median age was 67 yr (43–83) prior lines therapy 3 (1–10); follow-up 4.2 mo (0.1–10.4). TRAEs grade (Gr)/Gr ≥3 occurred 90%/48% pts; most common (any Gr TRAE ≥20% pts) were blurred vision (49%), keratopathy (44%), nausea (29%), fatigue (20%), AST increased keratitis (20%). higher that ≥5% (15%), (12%), neutropenia (10%). Ocular events led to treatment discontinuation 5 (8%) pts, treated at than 5.0 Unadjudicated pneumonitis/ILD reported 2 (3%) both leading discontinuation. Peripheral neuropathy 15%; all did not lead reduction No treatment-related death reported. 35 cMET+ (2+ ≥25% cells) 3.7 (0.7–10.3). ORR 38% post-baseline disease assessment (n=29). DCR 6 wk/12 wk/24 wk 97%/83%/53%. 44% Non-squamous (NSQ) EGFR wild-type (n=16), NSQ EGFR-mutant (n=8), 25% squamous cell carcinoma (n=4). Antitumor activity similar levels known cutoffs, no clear dose-response relationship observed ≥4.0mpk. Doses Q3W dose-break (2-on 1-off) 4.0 further evaluation expansion. Conclusions: well tolerated rates severity AEs commonly associated cytotoxic agents. Preliminary anti-tumor suggests can benefit cMET-expressing pts. Dose currently ongoing as January 2025. Clinical trial information: NCT05652868 .