BOSTON, July 22, 2026
Verastem Oncology has announced that the first patient has been dosed in the TARGET-D 202 Phase 2 registration-directed clinical trial evaluating VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor, for patients with previously treated KRAS G12D-mutated advanced non-small cell lung cancer (NSCLC). The study represents the company’s second registration-directed Phase 2 program for VS-7375 following the recent launch of the TARGET-D 201 pancreatic cancer trial. Approximately 5% of NSCLC patients harbor KRAS G12D mutations, yet no FDA-approved therapies currently exist that specifically target this mutation, highlighting a significant unmet medical need in precision oncology.
TARGET-D 202 Evaluates VS-7375 in Advanced NSCLC
The TARGET-D 202 (NCT07659782) study is a global, open-label Phase 2 registration-directed trial designed to evaluate VS-7375 monotherapy at the recommended Phase 2 dose of 900 mg once daily. The trial is enrolling patients with unresectable locally advanced or metastatic KRAS G12D-mutated NSCLC whose disease has progressed after platinum-based chemotherapy and anti-PD-(L)1 immunotherapy. In addition to assessing efficacy and safety, the study includes a dedicated cohort evaluating patients with asymptomatic untreated brain metastases, addressing one of the most challenging complications of metastatic lung cancer. The results are expected to support a potential regulatory submission for VS-7375 in this patient population if the trial achieves its objectives.
Broad Clinical Development Across KRAS G12D-Driven Tumors
The launch of TARGET-D 202 further expands Verastem’s comprehensive TARGET-D clinical development program, which aims to establish VS-7375 across multiple KRAS G12D-driven cancers. The company’s earlier Phase 1/2 TARGET-D 101 trial has already demonstrated encouraging anti-tumor activity, dose-dependent responses, favorable pharmacokinetics, and a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), metastatic colorectal cancer (mCRC), advanced NSCLC, and other solid tumors. Verastem plans to initiate TARGET-D 203, a registration-directed Phase 2 study in metastatic colorectal cancer, completing development programs across the three most common KRAS G12D-driven tumor types. Updated clinical data from ongoing studies are expected during the second half of 2026.
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FDA Fast Track Supports Development of VS-7375
VS-7375 is designed as a dual ON/OFF KRAS G12D inhibitor, enabling it to bind both the active and inactive forms of the mutant KRAS protein, potentially providing more complete suppression of tumor signaling than inhibitors targeting only one state. The investigational therapy has already received FDA Fast Track Designation for both KRAS G12D-mutated pancreatic cancer and advanced NSCLC, recognizing the urgent need for targeted treatment options in these cancers. KRAS G12D accounts for approximately 26% of all KRAS mutations and is frequently found in pancreatic, colorectal, endometrial, biliary tract, and lung cancers, yet no approved therapies specifically target this mutation. With multiple registration-directed studies now underway, Verastem Oncology is positioning VS-7375 as a potential first-in-class targeted therapy for patients with KRAS G12D-driven cancers, supporting the company’s broader strategy to develop innovative treatments for RAS/MAPK pathway-driven malignancies.
Source: Verastem Oncology press release
