Verastem Oncology Highlights Promising Preclinical Data and Multiple Abstract Presentations at AACR 2026
Verastem Oncology has announced the acceptance of multiple late-breaking and regular abstracts for presentation at the AACR Annual Meeting 2026, scheduled to take place from April 17–22, 2026, in San Diego. These presentations will showcase new preclinical findings centered on the company’s investigational drug candidate, VS-7375, a novel KRAS G12D dual ON/OFF inhibitor currently in clinical development.
Breakthrough in KRAS G12D Targeting
The primary focus of the presented research is VS-7375, an oral small molecule designed to inhibit both the active (“ON”) and inactive (“OFF”) states of the KRAS G12D protein. This mutation is one of the most common drivers of cancer, particularly in pancreatic, lung, and colorectal cancers. Unlike conventional KRAS inhibitors that target only one conformational state, VS-7375 demonstrates a dual-binding mechanism with high affinity and extended target engagement. This unique pharmacological property is believed to contribute to its enhanced anti-tumor activity.
According to preclinical findings, VS-7375 showed strong and durable tumor regression in KRAS G12D-mutated cancer models. Notably, when used in combination with PRMT5 inhibitors, the compound demonstrated significant efficacy in pancreatic cancer models characterized by MTAP deletion—a genetic alteration frequently associated with aggressive tumor behavior.
Superior Efficacy in Preclinical Models
The data presented highlight the superiority of VS-7375 over other KRAS-targeting agents. In multiple preclinical models, including pancreatic, lung, and colorectal cancers, VS-7375 achieved deeper and more sustained tumor regression compared to both KRAS G12D ON-only inhibitors and broader pan-RAS inhibitors.
In one key pancreatic cancer model (KP4), treatment with VS-7375 resulted in sustained tumor shrinkage over time. While comparator drugs such as zoldonrasib and daraxonrasib initially produced similar tumor reductions, their effects diminished after approximately 20 days, leading to tumor regrowth. By contrast, VS-7375 maintained its anti-tumor activity, with significantly reduced tumor volume observed even at later time points. These findings were supported by pharmacodynamic analyses showing prolonged pathway inhibition uniquely associated with VS-7375.
Late-Breaking Abstract Presentations
Two late-breaking abstracts will be presented during the “Experimental and Molecular Therapeutics” session at the AACR Annual Meeting:
- One study focuses on the combination of VS-7375 with PRMT5 inhibition in pancreatic cancer models, demonstrating strong and durable tumor regression.
- Another highlights the superior activity of VS-7375 compared to ON-only KRAS G12D inhibitors in preclinical pancreatic cancer settings.
These presentations emphasize the potential of dual ON/OFF inhibition as a next-generation therapeutic strategy for KRAS-driven cancers.
Regular Abstract Highlights
In addition to the late-breaking research, several regular abstracts have been accepted:
- A presentation under the “Novel Antitumor Agents” session will detail the broad anti-tumor activity of VS-7375, both as a monotherapy and in combination with other agents. The findings reinforce its potency across multiple KRAS G12D-mutant cancer types.
- Another abstract, part of the “Therapies Targeting Metastasis” session, explores combination approaches involving other investigational compounds such as VS-4718 and avutometinib. In BRAF-mutant cancer models, these combinations significantly delayed tumor onset, induced regression of established tumors—including brain metastases—and improved overall survival outcomes.
Scientific Leadership Perspective
Jonathan Pachter, Ph.D., Chief Scientific Officer at Verastem Oncology, emphasized the significance of these findings. He noted that the ability of VS-7375 to bind both active and inactive KRAS states differentiates it from existing therapies and contributes to its robust and sustained anti-tumor effects. This dual mechanism, combined with a long residence time on the target protein, positions VS-7375 as a potentially transformative treatment option for patients with KRAS G12D-mutated cancers.
Broader Research Context
The research presented at AACR builds upon earlier findings shared at the AACR Special Conference in Cancer Research: RAS Oncogenesis and Therapeutics, held in March 2026. During that meeting, Dr. Pachter delivered a plenary presentation detailing the anti-tumor efficacy of VS-7375, both as a standalone therapy and in combination with targeted agents. The consistency of results across multiple studies further validates the therapeutic potential of this investigational drug.
Implications for Cancer Treatment
KRAS mutations have long been considered difficult to target, earning the label of “undruggable” in oncology. However, recent advancements in targeted therapies have begun to change this narrative. VS-7375 represents a new wave of innovation aimed at overcoming the limitations of earlier KRAS inhibitors.
Its ability to deliver durable responses and overcome resistance mechanisms observed with other therapies could make it particularly valuable in treating cancers with high unmet medical needs, such as pancreatic cancer. Moreover, the promising results seen in combination therapies suggest that VS-7375 could play a central role in multi-agent treatment strategies designed to improve patient outcomes.
Looking Ahead
The upcoming presentations at AACR 2026 are expected to generate significant interest within the oncology community. As VS-7375 continues to advance through clinical development, further studies will be critical to confirming its safety and efficacy in human patients.
Verastem Oncology’s continued focus on RAS/MAPK pathway-driven cancers underscores its commitment to developing innovative therapies for patients with limited treatment options. The data presented at AACR not only highlight the potential of VS-7375 but also reinforce the broader promise of next-generation targeted cancer therapies.
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. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. Verastem initiated VS-7375-101, an international Phase 1/2 clinical trial, in June of 2025 in the U.S., that is evaluating the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. 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 (PDAC) and for the treatment of patients with KRAS G12D-mutated locally advanced or metastatic PDAC who have received at least one prior line of standard systemic therapy.
About the GenFleet Therapeutics Collaboration
The collaboration with GenFleet Therapeutics 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. Verastem selected VS-7375 (also known as GFH375), an oral KRAS G12D (ON/OFF) inhibitor, as its lead program in December 2023 and the license for VS-7375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside the GenFleet markets of mainland China, Hong Kong, Macau, and Taiwan.
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
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