FDA Grants Fast Track Designation to VS-7375 for KRAS G12D-Mutated Pancreatic Cancer

Verastem Oncology has announced that the FDA has granted fast track designation to VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor. This designation applies to 2 distinct indications for patients with KRAS G12D-mutated locally advanced or metastatic adenocarcinoma of the pancreas (PDAC): as a first-line treatment and for patients who have progressed after at least 1 prior line of standard systemic therapy.¹

The FDA’s decision underscores the urgent need for novel therapeutic strategies in pancreatic cancer, particularly for those harboring specific genetic mutations that have historically been challenging to target.

The fast track designation program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious conditions and have the potential to address unmet medical needs. The fast track designation for VS-7375 highlights its promising profile as a potential best-in-class KRAS G12D inhibitor, given the current absence of FDA-approved targeted therapies specifically addressing the KRAS G12D mutation. This mutation is prevalent in a significant subset of pancreatic cancers and is associated with aggressive disease and poor prognosis.

“The fast track designation for VS-7375 underscores the importance of our potential best-in-class KRAS G12D (ON/OFF) inhibitor. As we continue enrollment in our [US] phase 1/2a clinical trial [NCT07020221], our goal is to accelerate the program’s development given the lack of FDA-approved, KRAS G12D-targeted treatments for people living with KRAS G12D cancers,” said Dan Paterson, president and chief executive officer of Verastem Oncology, in a press release.

The unique mechanism of action of VS-7375, targeting both the ON and OFF states of the KRAS G12D protein, distinguishes it from other KRAS inhibitors that typically target only the OFF state. This dual targeting approach may offer a more comprehensive inhibition of KRAS signaling, potentially leading to improved clinical outcomes.

PDAC remains one of the most aggressive and challenging malignancies to treat, with a persistently low 5-year survival rate. The high prevalence of KRAS mutations, particularly G12D, in PDAC underscores the critical importance of developing effective targeted therapies.

The fast track designation for VS-7375 acknowledges its potential to fill a critical void in the treatment landscape for this patient population, particularly given the limited therapeutic options currently available for advanced PDAC.

The phase 1/2a clinical trial for VS-7375 is a multicenter study that aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of VS-7375 across various advanced solid tumors that harbor KRAS G12D mutations.² The study is enrolling patients across 5 sites in the US and is assessing VS-7375 as a monotherapy and in combination with cetuximab (Erbitux). The primary end points of parts A and B are safety, identifying the maximum tolerated dose, and evaluating preliminary anticancer activity of the optimal VS-7375 regimen, and in parts C and D they are identifying the recommended dose of VS-7375 in combination with cetuximab and identifying safety and preliminary efficacy of VS-7375 and cetuximab.

The FDA approved the investigational new drug application of VS-7375 in April 2025 after the agent was approved in China in June 2024.³

REFERENCES:

1. Verastem Oncology Granted Fast Track Designation for VS-7375 for the Treatment of KRAS G12D-mutated Locally Advanced or Metastatic Pancreatic Cancer. News release. Verastem Oncology. July 24, 2025. Accessed July 25, 2025. https://tinyurl.com/5e7ftfd9

2. A Phase 1/​2a Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors. ClinicalTrials.gov. Updated July 18, 2025. Accessed July 25, 2025. https://clinicaltrials.gov/study/NCT07020221

3. Verastem Oncology announces US IND clearance of VS-7375, oral KRAS G12D (ON/OFF) inhibitor, enabling phase 1/2a trial in advanced solid tumors. News release. Verastem Oncology. April 24, 2025. Accessed July 25, 2025. https://tinyurl.com/3db7zt28