BOSTON — Verastem Oncology has received U.S. Food and Drug Administration Fast Track designation for VS-7375, its investigational oral KRAS G12D inhibitor, for the treatment of certain adults with advanced non-small cell lung cancer.
The designation covers VS-7375 for adult patients with KRAS G12D-mutated unresectable locally advanced or metastatic non-small cell lung cancer who previously received platinum-based chemotherapy and an anti-PD-(L)1 antibody, either concurrently or sequentially.
VS-7375 is an oral, selective KRAS G12D inhibitor designed to bind both the active and inactive states of KRAS G12D. Verastem said the drug has the potential to inhibit KRAS G12D signaling and tumor growth more completely than compounds that block only one state of the target.
“Non-small cell lung cancer is the most prevalent lung disease with more than 8,000 patients in the U.S. diagnosed each year with KRAS G12D-mutations. Receiving Fast Track designation for VS-7375 reinforces both the significant unmet need and the potential of VS-7375 to improve outcomes for patients with KRAS G12D-mutated lung cancer,” said Michael Kauffman, M.D., Ph.D., president of development at Verastem Oncology. “We are continuing to accelerate the development of VS-7375 across multiple KRAS G12D-driven tumor types, including pancreatic, non-small cell lung, and colorectal cancers to bring a highly targeted, oral treatment option to patients as quickly as possible.”
The FDA previously granted Fast Track designation to VS-7375 for KRAS G12D-mutated advanced or metastatic pancreatic cancer.
Non-small cell lung cancer accounts for about 80% to 85% of all lung cancer cases. Most patients are diagnosed with advanced disease, including locally advanced or metastatic cancer that cannot be removed surgically. The KRAS G12D mutation occurs in about 5% of NSCLC cases and is associated with reduced responses to standard therapies and poor prognosis. No FDA-approved therapies currently specifically target KRAS G12D mutations in cancer.
Verastem has initiated TARGET-D 202, a Phase 2, open-label, multicenter study evaluating VS-7375 at a 900 mg once-daily oral dose in patients with advanced NSCLC who have received one to two prior lines of therapy. The study is also evaluating the drug in NSCLC patients with asymptomatic untreated brain metastases, based on positive preclinical data in intracranial tumor models.
In June 2025, Verastem began TARGET-D 101, a Phase 1/2 dose escalation, dose expansion and combination trial evaluating VS-7375 in patients with advanced KRAS G12D-mutated solid tumors, including pancreatic, non-small cell lung and colorectal cancers. Enrollment is ongoing.
The company said monotherapy dose escalation has progressed from 400 mg through 900 mg once daily without dose-limiting toxicities or major safety concerns observed to date. The study is currently evaluating a 1200 mg once-daily monotherapy dose and a 900 mg once-daily dose in combination with cetuximab.
Data reported in March 2026 from 23 patients treated across the 400 mg, 600 mg and 900 mg once-daily dose levels showed VS-7375 was generally well tolerated as of the Jan. 30, 2026, data cutoff. Verastem said no drug-related liver function test abnormalities or Grade greater than 2 neutropenia were observed, and reported rates of nausea, vomiting and diarrhea were lower than previously reported data from China.
Following FDA feedback, Verastem has expanded the VS-7375 clinical program with three Phase 2 registration-directed trials: TARGET-D 201 in metastatic pancreatic ductal adenocarcinoma, TARGET-D 202 in advanced non-small cell lung cancer and TARGET-D 203 in metastatic colorectal cancer.
KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The mutation is most common in pancreatic, colorectal, endometrial, biliary tract and non-small cell lung cancers.
Verastem selected VS-7375 as its lead program in December 2023 from its collaboration with GenFleet Therapeutics, which focuses on oncology discovery programs related to RAS/MAPK pathway-driven cancers. Verastem exercised its license for VS-7375 in January 2025, giving the company development and commercialization rights outside mainland China, Hong Kong, Macau and Taiwan. GenFleet is developing the drug as GFH375 in China.
