63A Phase 1/2 Study of VS-7375 in Advanced KRAS G12D-mt Solid Tumors, Including Cholangiocarcinoma

Background

Cholangiocarcinoma (CCA) is a global health problem with a rising incidence, accounting for approximately 10% of all primary liver cancers worldwide. Surgical resection remains the only potentially curative treatment; however, the majority of patients present with advanced-stage disease, thereby limiting curative options. As a result, there is a substantial unmet need for the development of effective systemic therapies.

Therapeutic strategies are increasingly focused on targeted approaches guided by next-generation sequencing. KRAS mutations are reported in approximately 20% of CCA cases, with KRAS G12D representing the most prevalent variant, accounting for roughly 40% of KRAS-mutant tumors. Here, we describe an ongoing Phase 1/2 study (NCT07020221) to assess the safety and efficacy of VS-7375, a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor, in patients with advanced KRAS G12D-mutated solid tumors, including cholangiocarcinoma.

Methods

Patient enrollment is currently ongoing in Part B3, in which the preliminary anticancer activity of VS-7375 (600 mg or 900 mg QD) is being assessed in patients with solid tumors, including cholangiocarcinoma. Eligible patients must have locally advanced unresectable or metastatic solid tumor harboring a KRAS G12D mutation. Key inclusion criteria include measurable disease according to RECIST vl.1, 1 or 2 prior lines of standard systemic therapy, ECOG performance status of 0 or 1, and adequate organ and cardiac function. Efficacy of the regimen will be evaluated through confirmed ORR, PFS rate, unconfirmed PR and CR rates, OCR, DOR, and PFS per RECIST vl.1.