Investigational Drug
VS-7375
TrialFetch AI Analysis
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Overview
VS-7375 (GFH375) is an investigational oral drug for cancers with a KRAS G12D mutation. Human results are available from a published phase 1 trial; a larger phase 2 lung-cancer update has also been reported, but the results below are from studies without a comparison group. (nature.com)
Mechanism of action
VS-7375 selectively inhibits KRAS G12D in both its active, GTP-bound (“ON”) and inactive, GDP-bound (“OFF”) states. Laboratory studies found that it interfered with KRAS G12D activation and its interaction with RAF1, a downstream signaling protein. (aacrjournals.org)
Efficacy
In a peer-reviewed phase 1 trial involving 74 previously treated patients, the confirmed objective response rate was 35.1% (13/37) among evaluable patients with pancreatic ductal adenocarcinoma and 35.7% (5/14) among those with non-small cell lung cancer (NSCLC). Median progression-free survival was 5.5 months in each group. (nature.com)
In a newer phase 2 NSCLC update reported by the developer, 71 patients had undergone a post-treatment assessment: the confirmed response rate was 52.1%, and the disease control rate was 93%. These figures are preliminary and come from a different patient group; they should not be read as a direct improvement over the phase 1 results. (genfleet.com)
Safety
In the published phase 1 trial, 27/74 patients (36.5%) had a grade 3 or higher treatment-related adverse event, and one patient (1.4%) had a treatment-related death reported as septic shock. No dose-limiting toxicities occurred among the 22 patients in dose escalation; 600 mg once daily was selected as the recommended phase 2 dose. The developer’s later NSCLC update identified diarrhea, vomiting and nausea as the most common treatment-related adverse events, mostly grade 1–2. (nature.com)
Further reading
- Peer-reviewed phase 1 trial, Nature Medicine
- Preclinical mechanism abstract, Cancer Research
- Developer-reported 2026 phase 2 NSCLC update
Last updated: Sep 2026
Active trials using VS-7375
Found 4 active trials using this drug:
TrialFetch AI summary: Patients with unresectable locally advanced or metastatic KRAS G12D-mutated NSCLC that has progressed after platinum chemotherapy and immune checkpoint inhibition receive daily oral VS-7375 monotherapy, an investigational inhibitor of both the active and inactive states of KRAS G12D. A dedicated cohort includes patients with untreated, asymptomatic brain metastases.
ClinicalTrials.gov ID: NCT07659782
TrialFetch AI summary: Adults with metastatic KRAS G12D-mutated colorectal adenocarcinoma and ECOG 0–1 receive investigational oral VS-7375, an inhibitor of active and inactive KRAS G12D. Previously treated patients receive it alone or with cetuximab or panitumumab; first-line patients receive it with cetuximab and mFOLFOX6.
ClinicalTrials.gov ID: NCT07659795
TrialFetch AI summary: Adults with metastatic KRAS G12D-mutated pancreatic ductal adenocarcinoma and ECOG 0–1 receive oral VS-7375, an investigational inhibitor of active and inactive KRAS G12D, alone or with the EGFR antibody cetuximab. Combination cohorts enroll patients in the first-line setting or after one prior metastatic regimen.
ClinicalTrials.gov ID: NCT07644559
TrialFetch AI summary: Adults with previously treated, unresectable or metastatic KRAS G12D-mutated solid tumors receive oral VS-7375, an investigational inhibitor of active and inactive KRAS G12D, alone or with the anti-EGFR antibody cetuximab. Expansion cohorts focus on pancreatic cancer and NSCLC for monotherapy and colorectal cancer for the combination; prior direct KRAS G12D inhibitor treatment is excluded.
ClinicalTrials.gov ID: NCT07020221
