BOSTON — Verastem Oncology said the first patient has been dosed in a Phase 2 registration-directed trial evaluating its investigational KRAS G12D inhibitor VS-7375 in previously treated advanced non-small cell lung cancer.
The global TARGET-D 202 trial will assess VS-7375 as a once-daily monotherapy at the recommended Phase 2 dose of 900 milligrams in patients with unresectable locally advanced or metastatic non-small cell lung cancer carrying a KRAS G12D mutation.
Eligible patients must have experienced disease progression after treatment with platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy.
The open-label study is designed to evaluate the drug’s safety and efficacy and potentially support a regulatory submission. A separate cohort will include patients with asymptomatic, untreated brain metastases.
Approximately 5% of patients with non-small cell lung cancer have a KRAS G12D mutation, but no therapies specifically targeting the mutation are currently approved by the U.S. Food and Drug Administration for this patient population, according to Verastem.
“Despite advances in RAS-targeted therapies, there are no FDA-approved therapies specifically designed to target KRAS G12D-mutated tumors,” said Michael Kauffman, M.D., Ph.D., President of Development at Verastem Oncology.
Kauffman said patients with KRAS G12D-mutated lung cancer continue to experience poor outcomes, with progression-free survival of about 11 months.
“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,” he said.
TARGET-D 202 is the second registration-directed Phase 2 trial underway for VS-7375. Verastem recently began dosing patients in TARGET-D 201, which is evaluating the drug in metastatic pancreatic cancer.
The company also plans to study VS-7375 in advanced metastatic colorectal cancer through the TARGET-D 203 trial.
VS-7375 is an oral inhibitor designed to target both the active and inactive forms of KRAS G12D. Verastem is developing the drug across several tumor types driven by the mutation.
In June 2025, the company began the TARGET-D 101 Phase 1/2 trial evaluating VS-7375 alone and in combination with other therapies in patients with pancreatic, colorectal and lung cancers, as well as other solid tumors carrying KRAS G12D mutations.
Verastem said early results from that study showed encouraging antitumor activity across multiple cancer types, evidence of greater activity at higher doses and a manageable safety profile.
The company expects to provide an updated analysis from TARGET-D 101 in the second half of 2026.
