BOSTON, July 28, 2026
Verastem Oncology announced that the first patient has been dosed in the TARGET-D 203 Phase 2 registration-directed clinical trial evaluating VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor, for patients with KRAS G12D-mutated metastatic colorectal cancer (mCRC). The milestone marks another major advancement in the company’s precision oncology pipeline, with all three TARGET-D Phase 2 registration-directed studies now actively enrolling patients across pancreatic, colorectal, and non-small cell lung cancers. TARGET-D 203 is designed to evaluate VS-7375 as both monotherapy and combination therapy with cetuximab or panitumumab in previously treated metastatic colorectal cancer, while an additional cohort will investigate VS-7375 combined with cetuximab and chemotherapy as a first-line treatment. Because KRAS G12D mutations occur in approximately 15% of metastatic colorectal cancer cases and currently lack FDA-approved targeted therapies, the trial addresses a significant unmet medical need in precision cancer treatment.
TARGET-D 203 Evaluates Multiple Treatment Strategies
The TARGET-D 203 (NCT07659795) study is an open-label, multicenter Phase 2 clinical trial evaluating 900 mg once-daily VS-7375 across multiple treatment settings. Researchers are assessing the investigational therapy both alone and in combination with anti-EGFR therapies, including cetuximab and panitumumab, for patients with previously treated KRAS G12D-mutated metastatic colorectal cancer. Another study cohort is exploring the combination of VS-7375, cetuximab, and chemotherapy in the frontline setting to determine whether earlier intervention can improve treatment outcomes. According to the company, preliminary findings from the ongoing TARGET-D 101 Phase 1/2 trial have demonstrated encouraging anti-tumor activity, evidence of dose-dependent efficacy, favorable pharmacokinetics, and a manageable safety profile across multiple KRAS G12D-driven cancers, including metastatic pancreatic ductal adenocarcinoma, metastatic colorectal cancer, and advanced non-small cell lung cancer. Patient follow-up continues across both monotherapy and combination cohorts, with additional clinical data expected during the second half of 2026.
KRAS G12D Represents a Major Unmet Need in Colorectal Cancer
KRAS G12D is recognized as the most common KRAS mutation in colorectal cancer, representing approximately 26% of all KRAS mutations across human cancers and occurring in nearly 15% of colorectal cancer patients. Individuals with this mutation generally experience poorer clinical outcomes than those with KRAS wild-type disease, highlighting the need for targeted treatment options. Despite substantial advances in colorectal cancer therapy, no FDA-approved treatments currently target KRAS G12D mutations specifically, leaving patients with limited therapeutic choices. Verastem believes VS-7375’s dual ON/OFF inhibition mechanism differentiates the therapy by targeting both the active and inactive forms of KRAS G12D, potentially providing more complete suppression of KRAS signaling and tumor growth than inhibitors that bind only one conformational state. The company also noted that the investigational therapy has received FDA Fast Track Designation for pancreatic cancer and non-small cell lung cancer indications, supporting accelerated development of the broader clinical program.
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Expanding Precision Oncology Across Multiple KRAS-Driven Cancers
The initiation of TARGET-D 203 further expands Verastem Oncology’s comprehensive TARGET-D clinical development program, which includes TARGET-D 201 for metastatic pancreatic cancer, TARGET-D 202 for advanced non-small cell lung cancer, and TARGET-D 203 for metastatic colorectal cancer. Together, these studies are evaluating VS-7375 across several of the most common KRAS G12D-driven malignancies, reinforcing the company’s commitment to advancing precision oncology therapies for genetically defined patient populations. By combining targeted molecular inhibition, combination treatment strategies, and registration-directed clinical development, Verastem aims to establish VS-7375 as a potential best-in-class oral KRAS G12D inhibitor capable of addressing significant unmet needs across multiple difficult-to-treat cancers. Successful outcomes from the ongoing Phase 2 trials could support future regulatory submissions and potentially introduce one of the first targeted treatment options specifically designed for KRAS G12D-mutated cancers.
Source: Verastem Oncology press release
