Verastem Oncology’s VS-7375 Receives FDA Fast Track Designation for KRAS G12D-Mutated Non-Small Cell Lung Cancer
Verastem Oncology, a biopharmaceutical company focused on developing targeted therapies for cancers driven by the RAS/MAPK signaling pathway, has announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to VS-7375, its investigational oral selective KRAS G12D (ON/OFF) inhibitor, for the treatment of adult patients with KRAS G12D-mutated, unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) following prior therapy with platinum-based chemotherapy and anti–PD-(L)1 immunotherapy.
The designation marks another important regulatory milestone for VS-7375 and underscores growing recognition of the urgent need for targeted treatment options in KRAS-driven cancers. The FDA previously granted Fast Track Designation for VS-7375 in metastatic pancreatic cancer, further expanding the potential clinical applications of the therapy across multiple tumor types.
Addressing a High-Unmet-Need Lung Cancer Subtype
Non-small cell lung cancer (NSCLC) represents the most common form of lung cancer, accounting for approximately 80% to 85% of all lung cancer cases. A large proportion of patients are diagnosed at advanced stages, including locally advanced or metastatic disease, which is generally not amenable to surgical intervention and carries a poor prognosis.
Within this broad disease category, KRAS mutations are among the most important oncogenic drivers. The KRAS G12D mutation occurs in approximately 5% of NSCLC cases, and patients with this alteration typically experience limited responses to standard-of-care therapies and significantly worse clinical outcomes.
Despite advances in targeted oncology, there are currently no FDA-approved therapies specifically designed to inhibit KRAS G12D, leaving a major therapeutic gap in lung cancer treatment. VS-7375 is designed to address this unmet need as a selective, oral small molecule inhibitor targeting KRAS G12D in both its active (ON) and inactive (OFF) states, a mechanism intended to suppress tumor signaling more effectively across dynamic tumor biology.
Fast Track Designation and Its Significance
FDA Fast Track Designation is intended to expedite the development and regulatory review of therapies that address serious or life-threatening conditions and demonstrate the potential to fulfill an unmet medical need. For investigational therapies such as VS-7375, this designation may provide several development advantages, including more frequent interactions with the FDA, eligibility for rolling review of a New Drug Application (NDA), and potential eligibility for priority review or accelerated approval if regulatory criteria are met.
According to Verastem Oncology leadership, the designation highlights both the seriousness of KRAS G12D-mutated NSCLC and the potential of VS-7375 to meaningfully improve outcomes in this patient population.
Clinical Development Strategy Expands Across Multiple Tumor Types
Verastem Oncology is advancing VS-7375 through a broad clinical development program targeting multiple KRAS G12D-driven cancers, including non-small cell lung cancer, pancreatic ductal adenocarcinoma, and colorectal cancer. These tumor types are among the most aggressive solid malignancies and share a common dependence on KRAS signaling pathways.
The company is currently evaluating VS-7375 in several ongoing and planned clinical studies designed to support both dose optimization and later-stage regulatory development.
TARGET-D 202: Focus on Advanced NSCLC
The TARGET-D 202 trial is a Phase 2, open-label, multi-center study evaluating VS-7375 in patients with advanced NSCLC who have received one to two prior lines of therapy. Patients in the study are receiving an oral dose of 900 mg once daily (QD).
Importantly, based on preclinical evidence demonstrating activity in intracranial tumor models, the trial is also enrolling NSCLC patients with asymptomatic, untreated brain metastases, an area of high unmet need in lung cancer care due to limited therapeutic penetration into the central nervous system and poor prognosis associated with brain involvement.
TARGET-D 101: Early Clinical Activity Across Solid Tumors
Verastem initiated the TARGET-D 101 study in June 2025 as 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, lung, and colorectal cancers.
The study is currently assessing multiple dosing cohorts ranging from 400 mg to 1200 mg once daily, as well as combination regimens such as a 900 mg dose combined with cetuximab. According to the company, dose escalation has proceeded without dose-limiting toxicities or major safety concerns observed to date.
In March 2026, Verastem reported early clinical data from 23 patients treated across the 400 mg, 600 mg, and 900 mg dose levels. The median treatment duration was approximately 1.6 months, ranging from 0.7 to 5.6 months. The safety profile was described as generally favorable, with no drug-related liver function abnormalities or Grade 3 or higher neutropenia observed as of the latest data cutoff.
Additionally, patients experienced comparatively lower rates of common gastrointestinal side effects such as nausea, vomiting, and diarrhea relative to earlier external datasets reported in China, suggesting a potentially improved tolerability profile.
Advancing Toward Registration-Directed Studies
Following regulatory feedback from the FDA, Verastem has expanded its clinical program to include three registration-directed Phase 2 trials designed to support potential future regulatory submissions:
- TARGET-D 201 in metastatic pancreatic ductal adenocarcinoma
- TARGET-D 202 in advanced non-small cell lung cancer
- TARGET-D 203 in metastatic colorectal cancer
These trials represent a strategic step toward late-stage development of VS-7375 across multiple high-incidence KRAS G12D-driven cancers. The company’s goal is to generate robust clinical data supporting both efficacy and safety across tumor types that share a common oncogenic driver but differ in tumor microenvironment and treatment resistance mechanisms.
Company Perspective on Unmet Need and Development Acceleration
Verastem Oncology leadership emphasized the urgency of developing effective therapies for KRAS G12D-mutated cancers, particularly in NSCLC where patient outcomes remain poor despite advances in immunotherapy and chemotherapy combinations.
The company noted that KRAS G12D mutations represent a significant subset of lung cancer cases and are associated with aggressive disease biology and limited responsiveness to existing treatment options. As a result, there is a critical need for targeted therapies that can directly inhibit oncogenic KRAS signaling.
The Fast Track Designation is expected to accelerate VS-7375 development by enabling more frequent regulatory engagement and potentially streamlining the path toward later-stage clinical trials and eventual approval.
Broader Implications for KRAS-Targeted Oncology
KRAS mutations have long been considered among the most challenging targets in oncology due to the protein’s structure and role in fundamental cellular signaling pathways. While recent advances have led to approved therapies targeting KRAS G12C mutations, KRAS G12D remains one of the most prevalent and difficult-to-target variants, particularly in pancreatic and colorectal cancers as well as subsets of lung cancer.
VS-7375 represents part of a new generation of investigational therapies designed to expand KRAS targeting beyond G12C, potentially addressing a broader patient population with limited treatment options.
If successful, selective KRAS G12D inhibition could significantly reshape treatment paradigms across multiple tumor types, offering a precision medicine approach where none currently exists.
The FDA’s Fast Track Designation for VS-7375 underscores the urgent need for new therapies in KRAS G12D-mutated non-small cell lung cancer and highlights the potential of Verastem Oncology’s investigational inhibitor to address a major gap in oncology treatment.
With ongoing Phase 1/2 studies demonstrating early signs of tolerability and expanding Phase 2 registration-directed trials underway, VS-7375 is advancing rapidly through clinical development. As data continue to mature across NSCLC, pancreatic, and colorectal cancers, the program is positioned to play a potentially important role in the future of targeted cancer therapy.
About KRAS G12D
KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), 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
VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. The mechanism of action of VS-7375 is unique in that it binds 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 advanced KRAS G12D mutant 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 in second-line advanced or metastatic pancreatic ductal carcinoma, TARGET-D 202 in second/third-line advanced or metastatic non-small cell lung cancer, and TARGET-D 203 in metastatic colorectal cancer.
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 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.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a biopharmaceutical company committed to developing and commercializing new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Verastem markets AVMAPKI® FAKZYNJA® CO-PACK in the U.S. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition, and KRAS G12D inhibition.
