On July 22, 2026 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported that the first patient has been dosed in the TARGET-D 202 Phase 2 registration-directed trial evaluating VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor, in patients with previously treated KRAS G12D-mutated advanced non-small cell lung cancer (NSCLC). The initiation of TARGET-D 202 marks the second registration-directed Phase 2 clinical trial now underway for VS-7375, following first-patient dosing in the TARGET-D 201 metastatic pancreatic cancer study announced last month.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Despite advances in RAS-targeted therapies, there are no FDA-approved therapies specifically designed to target KRAS G12D-mutated tumors. Among the many challenges facing patients with KRAS G12D-mutated lung cancer, they continue to experience some of the poorest outcomes with progression-free survival of approximately 11 months – shorter than those with other common KRAS mutations," said Michael Kauffman, M.D., Ph.D., president of development at Verastem Oncology. "We’re making significant progress with the TARGET-D clinical trial programs, and once the first patient is dosed in the TARGET-D 203 Phase 2 study for advanced metastatic colorectal cancer, we will have registration-directed trials underway across the three most common KRAS G12D-driven tumor types. We believe we are well positioned to advance the broad clinical development of VS-7375 across multiple tumor types to selectively target KRAS G12D to maximize efficacy, allow for tolerable combinations, and avoid toxicities problematic with non-specific pan-RAS inhibitors."
TARGET-D 202 (NCT07659782) is a global, open-label, Phase 2 registration-directed trial evaluating VS-7375 monotherapy at the recommended Phase 2 dose (RP2D) of 900 mg daily (QD) in patients with unresectable locally advanced or metastatic KRAS G12D-mutated NSCLC whose disease has progressed following prior treatment with platinum-based chemotherapy and an anti-PD-(1) therapy. The trial is designed to evaluate the efficacy and safety of VS-7375 and support a potential registration strategy in this patient population. A cohort in the study will also evaluate VS-7375 in non-small cell lung cancer patients with asymptomatic untreated brain metastases.
In June 2025, Verastem initiated TARGET-D 101, its Phase 1/2 dose escalation, dose expansion, and combination clinical trial evaluating the safety and efficacy of VS-7375 in patients with KRAS G12D-mutated metastatic pancreatic ductal carcinoma (mPDAC), metastatic colorectal cancer (mCRC), NSCLC, and other solid tumor cancers. In a recent update, the Company shared that VS-7375 demonstrated encouraging anti-tumor activity across multiple KRAS G12D-driven tumor types, including mPDAC, mCRC, and advanced NSCLC, with evidence of dose-dependent activity, favorable PK supporting target exposure, and a favorable and manageable safety and tolerability profile. Patient follow-up continues to mature across monotherapy and combination cohorts, and the Company expects to share an update in the second half of 2026.
About Non-Small Cell Lung Cancer
Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 80–85% of all lung cancer diagnoses. Approximately 10,000 patients with NSCLC harbor a KRAS G12D mutation in the U.S. annually. Compared with other KRAS mutation variants, metastatic KRAS G12D NSCLC is associated with the shortest progression-free survival and has been linked to immune suppression and resistance to anti-PD-(L)1 therapies. KRAS G12D is the most common KRAS mutation among never-smokers, while also occurring in many patients with a history of smoking. Additionally, brain metastases remain a significant clinical challenge in metastatic NSCLC, affecting approximately 10–20% of patients at diagnosis and up to 40% during the course of disease. Despite these challenges and the significant unmet medical need, there are currently no approved therapies specifically targeting KRAS G12D-mutated NSCLC.
About KRAS G12D
KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. When the KRAS gene is mutated, it can promote cancer development and growth. Patients with KRAS G12D-mutant tumors often have poorer outcomes, underscoring the need for therapies designed specifically to inhibit this mutation potently and for a long duration. The KRAS G12D mutation occurs most commonly in pancreatic (40%), colorectal (15%), endometrial (8%), biliary tract (7-15%), and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) specifically targeting KRAS G12D mutations in cancer.
About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor & TARGET-D Clinical Program
VS-7375 is a potential best-in-class, potent, and selective investigational oral KRAS G12D dual ON/OFF inhibitor. It is designed to uniquely bind to both the active (ON) and inactive (OFF) states of KRAS G12D, with the potential to inhibit KRAS G12D signaling and tumor growth more completely than compounds that block KRAS G12D only in the OFF state or only in the ON state.
In June 2025, Verastem initiated TARGET-D 101, a Phase 1/2 dose escalation, dose expansion, and combination clinical trial evaluating the safety and efficacy of VS-7375 in patients with KRAS G12D-mutated metastatic pancreatic ductal carcinoma (mPDAC), metastatic colorectal cancer (mCRC), advanced non-small cell lung cancer (NSCLC), and other solid tumors. Verastem has further expanded the VS-7375 clinical program with the initiation of three Phase 2 registration-directed, open-label clinical trials: TARGET-D 201 (NCT07644559) in second-line advanced or metastatic PDAC, TARGET-D 202 (NCT07659782) in second/third-line advanced or metastatic NSCLC, and TARGET-D 203 (NCT07659795) in metastatic CRC. In June 2026, the company announced the first patient was dosed in the TARGET-D 201 trial.
In July 2025, U.S. Food and Drug Administration (FDA) granted Fast Track Designation (FTD) to VS-7375 for the first-line treatment of patients with KRAS G12D-mutated locally advanced or metastatic adenocarcinoma of the pancreas and for the treatment of patients with KRAS G12D-mutated locally advanced or metastatic pancreatic ductal carcinoma who have received at least one prior line of standard systemic therapy. In June 2026, the FDA also granted FTD to VS-7375 for the treatment of adult patients with KRAS G12D-mutated unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received platinum-based chemotherapy and an anti-PD-(L)1 antibody either concurrently or sequentially.
In December 2023, Verastem selected VS-7375 as its lead program from its collaboration with GenFleet Therapeutics, which aims to advance three oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase 1 trial. In January 2025, Verastem exercised its license for VS-7375. The licenses would give Verastem development and commercialization rights outside the GenFleet markets of mainland China, Hong Kong, Macau, and Taiwan. GenFleet is developing VS-7375 as GFH375 in China.
(Press release, Verastem, JUL 22, 2026, View Source [SID1234669370])