Preliminary interim data of elzovantinib (TPX-0022), a novel inhibitor of MET/SRC/CSF1R, in patients with advanced solid tumors harboring genetic alterations in MET: Update from the Phase 1 SHIELD-1 trial

Background: Elzovantinib is a novel, type I tyrosine kinase inhibitor (TKI) that targets MET, SRC, and CSF1R. Genetic alterations in including exon 14 skipping (Δex14) mutations other oncogenic mutations, amplifications, fusions are present many tumor types. The Phase 1 SHIELD-1 trial (NCT03993873) evaluating safety, pharmacokinetics (PK), preliminary activity of elzovantinib patients (pts) with advanced solid tumors harboring genetic MET alterations. An early analysis included 46 efficacy evaluable pts. Among 32 TKI-naïve pts, 8 had confirmed PRs, 4 NSCLC, 3 gastric/GE junction adenocarcinomas, colorectal cancer (Hong DS, et al. EORTC-NCI-AACR 2021, Poster nr P225). Here we report updated data from SHIELD-1. Patients methods: Adults were enrolled using 3+3 dose-escalation design additional pt enrollment at doses where clinical was observed. Dose expansion the RP2D 40 mg QD to BID titration dose enrolling pts results this portion study will be available for presentation. given orally continuous 28-day cycles. Results: As 13 May 2022, 59 have been across levels phase, 33 NSCLC (21 Δex14, 9 mutations), gastric (8 fusion), 17 who cancers Median age 63 (33–84) years. number prior therapies 2 (range 0–7). 39 (66%: 15 NSCLC; gastric; others) not received therapy 20 (34%: 18 liver; pancreatic) therapy. most common adverse events (AEs) dizziness (68%), fatigue (41%), anemia (36%), constipation (34%), lipase increase (32%). Most AEs low-grade, 95% being Grade or 2. No interstitial lung disease/pneumonitis, 3/4 edema, treatment-related ALT/AST elevation reported. Systemic exposure increased dose-dependent manner. Evaluation recommended (RP2D) ongoing safety analyses Conclusions: Elzovantinib, novel MET/SRC/CSF1R inhibitor, generally well tolerated primarily low-grade dizziness, no high-grade favorable PK profile. currently under evaluation A global multi-cohort MET-altered planned. Conflict interest: Advisory Board: Drs. Bazhenova Falchook: Turning Point Therapeutics, Inc. Corporate-sponsored Research: Hong, Shergill, Heist, Moreno, Falchook, Besse, Kim: Other Substantive Relationships: Ms. Zhao, Atwal, Park: Employment, Stock ownership –