FDA Clears IND for VS-7375 in KRAS 612D-Mutated Advanced Solid Tumors
The clearance precedes the initiation of a phase 1/2a trial that will evaluate the efficacy and safety of VS-7375 in advanced solid tumors with a KRAS-612D mutation.
The results of VS-7375 in advanced solid tumors from a phase 1/2a trial will be reported at the 2025 ASCO Annual Meeting.
The US FDA has cleared the investigational new drug (IND) application for VS-7375, an oral KRAS 612D inhibitor, in the treatment of patients with advanced solid tumors, according to a press release from the developer, Verastem Oncology.1
The clearance of the IND precedes the developer’s initiation of a phase 1/2a trial (NCT06500676) in the middle of 2025. Currently, there are plans for the trial to include various expansion cohorts including pancreatic cancer, colorectal cancer, and non–small cell lung cancer; it will also include drug combinations.
An abstract on the preliminary dose escalation phase of the phase 1/2 trial has been accepted for rapid oral presentation at the 2025 American Society of Clinical Oncology Annual Meeting on May 30 to June 3. Additional data will be shared after the embargo is lifted on May 22, 2025, at 5 pm EDT. The abstract 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 trial will be multicenter and open-label, and will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of VS-7375 in patients with KRAS G12D-mutant advanced solid tumors.2
Previously, in June 2024, VS-7375 was approved in China; the first patient was dosed in July 2024 in a phase 1/2 study.3
“We’re excited to advance the clinical program for VS-7375 in the US and build on the initial dose escalation work conducted by GenFleet in China that demonstrated oral bioavailability and no dose-limiting toxicities across 6 dose levels, with partial responses achieved among multiple patients with both pancreatic and advanced lung cancers,” Dan Paterson, president and chief executive officer of Verastem Oncology, stated in the press release.1 “We believe there remains a significant opportunity to improve on the efficacy seen to date with other KRAS G12D-selective agents. VS-7375’s dual inhibition of both the ON/OFF states has the potential to drive deep and durable cancer responses and allow for better combinability with other agents.”
The trial will be held in the US, and the starting dose for phase 1 comes from the efficacious dose identified in the initial data from a GenFleet study. Dose escalation will occur across all dose levels where activity and cancer responses were observed. The phase 2a portion of the trial will assess the efficacy and safety of the agent as monotherapy and in combination with other drugs.
Eligible patients are to be 18 years or older and 75 years or younger with histologically or cytologically confirmed advanced or metastatic solid tumors with a KRAS G12D mutation.1 Additionally, patients must have an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1, a life expectancy of at least 12 weeks, and adequate laboratory parameters.
Exclusion criteria include having active brain metastases, prior treatment with a KRAS G12D inhibitor, poorly controlled or severe cardiovascular disease, active hepatitis B or hepatitis C, and palliative radiotherapy completed within 14 days of the first study dose.
In the phase 1a portion, the primary outcomes are the incidence and severity of adverse effects (AEs) and serious adverse effects (SAEs), and the incidence of dose-limiting toxicities; in the phase 1b portion, it was the incidence and severity of AEs and SAEs; and in the phase 2 portion, it was overall response rate per RECIST v1.1.
“We look forward to our partner GenFleet’s oral presentation that will include updated safety and efficacy data from the Phase 1 study at the ASCO annual meeting,” concluded Paterson.1
References
- Verastem Oncology announces U.S. 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 23, 2025. Accessed April 24, 2025. https://tinyurl.com/ytyszczx
- A study of GFH375 in patients with advanced solid tumors with KRAS G12D mutations. ClinicalTrials.gov. Updated April 2, 2025. Accessed April 24, 2025. https://tinyurl.com/ez7jfun5
- Verastem Oncology announces first patient dosed with GFH375/VS-7375, a KRAS G12D (ON/OFF) inhibitor, in a phase 1/2 trial in China as part of collaboration with GenFleet Therapeutics. News release. Verastem Oncology. July 12, 2024. Accessed April 24, 2025. https://tinyurl.com/2ecvmhen
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