Verastem Gets U.S. IND Clearance for KRAS G12D Inhibitor VS-7375, Paving Way for Phase 1/2a Trial in Solid Tumors
Verastem Oncology (Nasdaq: VSTM), a Boston-based biopharmaceutical company at the forefront of developing precision oncology therapies, has announced a significant milestone in its mission to combat RAS/MAPK pathway-driven malignancies. On April 24, 2025, the company revealed that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for VS-7375, a highly selective and potent oral KRAS G12D (ON/OFF) inhibitor. This regulatory green light paves the way for the launch of a Phase 1/2a clinical study in mid-2025, targeting several aggressive and hard-to-treat solid tumors.
KRAS G12D mutations are among the most common and challenging genetic alterations in oncology, particularly prevalent in pancreatic, colorectal, and non-small cell lung cancers (NSCLC). These malignancies are frequently associated with poor prognoses and limited treatment options. As such, the development of VS-7375 represents a major stride in addressing an area of high unmet medical need. Verastem’s innovative candidate aims to tackle the KRAS G12D mutation through dual inhibition of both its active (“ON”) and inactive (“OFF”) states—a novel approach that could potentially overcome the resistance limitations observed with earlier generation KRAS inhibitors.
A New Era for KRAS G12D Mutant Solid Tumors
The upcoming Phase 1/2a clinical trial of VS-7375 will be conducted initially within the United States, with the potential for global expansion. The trial is designed to assess both the safety and anti-tumor activity of the compound in patients with advanced solid tumors harboring the KRAS G12D mutation. These include some of the most lethal cancers—pancreatic ductal adenocarcinoma, metastatic colorectal cancer, and non-small cell lung cancer—where survival rates remain dismally low and therapeutic breakthroughs are desperately needed.
In a strategic move to accelerate the clinical program, Verastem plans to begin dosing at levels informed by prior preclinical and clinical data obtained through its collaboration with Shanghai-based GenFleet Therapeutics. This partner-led study, conducted in China, has already completed its dose escalation phase, which provided encouraging initial results that will be further expanded upon at the upcoming 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
Promising Early Results from GenFleet’s Chinese Trial
The foundational data supporting Verastem’s U.S. IND filing stems from the first-in-human study of VS-7375 (also referred to as GFH375) conducted by GenFleet. During this trial, VS-7375 demonstrated favorable oral bioavailability and an encouraging safety profile, with no dose-limiting toxicities observed across six dose levels. Notably, preliminary clinical activity was reported, with partial responses seen in patients with advanced pancreatic and lung cancers—tumor types notoriously difficult to treat.
Dan Paterson, President and Chief Executive Officer of Verastem Oncology, expressed optimism about the implications of these early findings. “We’re excited to advance the clinical program for VS-7375 in the U.S. and build on the initial dose escalation work conducted by GenFleet in China,” Paterson stated. “The preliminary data suggest that VS-7375 is not only well-tolerated but also biologically active in a subset of patients who have limited therapeutic options. We believe there remains a significant opportunity to improve upon the efficacy seen to date with other KRAS G12D-selective agents.”
He further highlighted the unique mechanism of action of VS-7375: “Its dual inhibition of both the ON and OFF states of KRAS G12D could translate into deeper and more durable responses in patients. Furthermore, this pharmacologic profile may allow for improved combination potential with other targeted agents or immunotherapies, a strategy we plan to explore in our Phase 2a cohorts.”
ASCO 2025: Global Spotlight on GFH375
Adding momentum to the program, Verastem also announced that GenFleet’s abstract detailing the dose escalation findings from the GFH375 Phase 1/2 study has been accepted for rapid oral presentation at the prestigious ASCO 2025 Annual Meeting. The presentation is scheduled to take place on Monday, June 2, 2025, from 8:00 to 9:30 a.m. Central Daylight Time, as part of the “Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology” session.
The abstract, which remains under embargo until May 22, 2025, at 5:00 p.m. Eastern Time, is titled “A First-in-Human Phase I/II Study of GFH375, a Highly Selective and Potent Oral KRAS G12D Inhibitor in Patients with KRAS G12D Mutant Advanced Solid Tumors.” The oral presentation will provide the oncology community with updated safety, pharmacokinetic, and preliminary efficacy data—insights that are eagerly anticipated by stakeholders across the global oncology landscape.
Strategic Vision: Building on Foundational Science
The advancement of VS-7375 into clinical development in the United States exemplifies Verastem’s strategic focus on targeted oncology innovation. By concentrating on cancers driven by defined genetic mutations such as KRAS G12D, the company aims to deliver highly precise therapeutics that can offer meaningful clinical benefits in tumor types that have historically shown resistance to standard treatments.
Moreover, Verastem’s collaborative approach—leveraging early-stage development from international partners like GenFleet—has enabled the company to de-risk clinical advancement and strategically position its investigational therapies within competitive global oncology markets. With the KRAS inhibitor space rapidly evolving, driven by landmark approvals of drugs targeting KRAS G12C mutations, the industry has turned its attention to the next frontier: G12D. VS-7375 could be poised to lead this charge.
As Verastem prepares for clinical site activation and patient enrollment in mid-2025, the company’s leadership remains focused on executing a data-driven development strategy. The Phase 2a portion of the study will be particularly critical, as it aims to explore the potential of VS-7375 in both monotherapy settings and in rational combinations with other anti-cancer agents. By doing so, Verastem seeks not only to enhance response rates but also to improve durability and quality of life for patients battling KRAS-driven malignancies.
With the spotlight set on ASCO 2025, all eyes will be on GFH375’s clinical performance and its potential to redefine outcomes in KRAS G12D mutant cancers. The oncology field is hungry for innovation—and Verastem, through its bold scientific pursuits and collaborative model, is rising to meet that challenge head-on.
