A Phase 1/2, Open-label Study of VS-7375, a KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and in Combination, in Patients with Advanced KRAS G12D-Mutant Solid Tumors

Condition studied

Advanced KRAS G12D-Mutant Solid Tumors

Investigational medicinal product(s)

Eligibility

Primary endpoint

Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and DLTs; and abnormal vital signs, physical examination, ECG parameters, ECOG PS, clinical laboratory results; and dose interruptions/reductions., Proportion/number of participants with DLTs during the DLT assessment period (C1D1 through C1D21)., Confirmed ORR by blinded independent central review (BICR) per RECIST v1.1., Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and DLTs; and abnormal vital signs, physical examination, ECG parameters, ECOG PS, clinical laboratory results; and dose interruptions/reductions., Proportion/number of participants with DLTs during the DLT assessment period (through C1)., Confirmed ORRby BICR, per RECIST v1.1., AUC0-t, AUC0-inf, and Cmax of midazolam, repaglinide and relative metabolites., Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs; and abnormal vital signs, physical examination, ECG parameters, ECOG PS, clinical laboratory results; and dose interruptions/reductions.

Endpoint detail

PK parameters derived from plasma concentrations of VS-7375 including Cmax and AUC., Confirmed ORR, DCR, and DOR per RECIST v1.1. Unless otherwise specified, all tumor response-based endpoints will be analyzed using both BICR and Investigator assessments., Confirmed ORR by Investigator-assessed DOR, BoR, DCR, PFS per RECIST 1.1 and OS., Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and abnormal vital signs, physical examination, ECG parameters, ECOG PS, clinical laboratory results; and dose interruptions/reductions., PK parameters derived from plasma concentrations of VS-7375 including Cmax and AUC, Change in nab-paclitaxel exposures in the presence and absence of VS-7375.