BOSTON, June 16, 2026
Verastem Oncology announced that the first patient has been dosed in the TARGET-D 201 Phase 2 registration-directed clinical trial evaluating VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor, for patients with KRAS G12D-mutated metastatic pancreatic ductal adenocarcinoma (mPDAC). The study represents a significant milestone in the clinical development of VS-7375, which has already received U.S. FDA Fast Track Designation for advanced or metastatic pancreatic cancer harboring KRAS G12D mutations. Designed to evaluate the therapy as both a monotherapy and in combination with cetuximab, the Phase 2 trial aims to provide registration-supporting data for patients with limited treatment options. The study also includes a frontline treatment cohort investigating a potential chemotherapy-free regimen, highlighting the company’s strategy to expand targeted treatment options for one of the deadliest forms of cancer.
TARGET-D 201 Evaluates VS-7375 Across First- and Second-Line Treatment Settings
The TARGET-D 201 (NCT07644559) study is a Phase 2, open-label, multicenter, registration-directed clinical trial evaluating 900 mg once-daily VS-7375 both as a standalone treatment and in combination with full-dose cetuximab in patients with second-line metastatic pancreatic cancer carrying the KRAS G12D mutation. In addition, a dedicated study cohort is evaluating the combination therapy as a first-line treatment, offering the possibility of a chemotherapy-free therapeutic approach. KRAS G12D is the most common KRAS mutation in pancreatic cancer, occurring in approximately 40% of patients, and is frequently associated with aggressive disease progression and poor clinical outcomes. Currently, no FDA-approved therapies specifically target KRAS G12D mutations, making the development of selective inhibitors a major priority in precision oncology. Verastem believes VS-7375’s ability to inhibit both the active (ON) and inactive (OFF) forms of KRAS G12D may provide more comprehensive suppression of tumor signaling than single-state inhibitors currently under development.
Clinical Development Expands Across Multiple KRAS G12D-Driven Cancers
The initiation of TARGET-D 201 follows ongoing progress in the broader TARGET-D clinical development program. Since launching the TARGET-D 101 Phase 1/2 trial in 2025, Verastem has reported continued dose escalation without dose-limiting toxicities or significant safety concerns, with patients currently receiving doses up to 1,200 mg once daily as monotherapy alongside combination studies with cetuximab, gemcitabine plus nab-paclitaxel, and carboplatin, pemetrexed, and pembrolizumab. Building on these findings, the company has expanded development into three registration-directed Phase 2 studies, including TARGET-D 201 for metastatic pancreatic cancer, TARGET-D 202 for advanced non-small cell lung cancer (NSCLC), and TARGET-D 203 for metastatic colorectal cancer. The investigational therapy has received FDA Fast Track Designation for both pancreatic cancer and NSCLC, supporting accelerated regulatory interactions for indications with significant unmet medical needs.
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VS-7375 Targets One of Oncology’s Most Challenging Genetic Mutations
Pancreatic cancer remains among the most lethal malignancies worldwide, with metastatic disease carrying an estimated five-year survival rate of only 3% despite advances in chemotherapy and targeted therapies. More than 90% of pancreatic cancers harbor KRAS mutations, with KRAS G12D representing the most prevalent subtype. Beyond pancreatic cancer, KRAS G12D mutations are also found in colorectal, non-small cell lung, endometrial, and biliary tract cancers, highlighting the potential for broad clinical application of targeted therapies. VS-7375 is designed as a dual ON/OFF KRAS G12D inhibitor, enabling continuous suppression of mutant KRAS signaling regardless of its activation state. With multiple registration-directed Phase 2 trials now underway, encouraging early safety findings, and ongoing FDA Fast Track support, Verastem Oncology continues advancing VS-7375 as a potential first-in-class targeted therapy for patients with KRAS G12D-mutated cancers, where effective treatment options remain extremely limited.
Source: Verastem Oncology press release
