A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Colorectal Cancer

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Histopathology confirmed metastatic CRC
• Measurable disease per RECIST 1.1
• Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing)
• ECOG PS=0 or 1
• 2L+ patients:
• Must have received at least 1 standard chemotherapy for metastatic colorectal adenocarcinoma
• Have documented disease progression during or following their most recent prior line of therapy
• Have either stable disease, partial response (PR), or complete response (CR) by RECIST v1.1 as the best overall response (BOR) during at least 1 prior systemic therapy.
• 1L patients:
• Treatment-naïve or received no more than 1 cycle of standard systemic therapy for metastatic disease.

You cannot join if

• Have any other documented co-existing common RAS mutation(s)
• Prior anti-cancer Tx within 4 weeks or drug-specific timeline within first treatment dose, whichever shorter
• Major surgery within 4 weeks of first treatment dose
• Radiation therapy (RT) within 1 week of first treatment dose
• Receipt of prior direct RAS inhibitor
• Receipt of more than 1 investigational therapy
• Untreated or symptomatic CNS metastasis
• Receipt of strong CYP3A4 inhibitor/inducer or CYP3A4 sensitive substrates with narrow therapeutic index within 14 days or drug-specific timeline within first treatment dose, whichever is shorter
• Receipt of PPI or H2 blocker within 5 days
• Inability to swallow oral medication
• Other protocol-defined inclusion/exclusion criteria may apply

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Treatments listed in the registry

• VS-7375 (Drug): Taken by mouth
• cetuximab (Drug): Intravenous infusion
• panitumumab (Drug): Intravenous infusion
• Cetuximab + mFOLFOX6 (Drug): Intravenous infusion

Randomized · Crossover · masking: Single

Main goals

• Confirmed ORR by blinded independent central review (BICR) per RESIST v1.1 - 2L CRC only (6 months)
• To characterize the safety and tolerability of VS-7375 monotherapy or in combination with cetuximab or panitumumab, administered on a daily oral schedule in participants with KRAS G12D-mutated 2L+ CRC (6 months)
• To characterize the safety and tolerability of VS-7375 in combination with cetuximab + mFOLFOX, administered on a daily oral schedule in participants with KRAS G12D-mutated 1L CRC (6 months)

Other goals

• Confirmed ORR per RECIST v1.1 assessed by BICR (primary) and Investigator (secondary) assessments
• Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, Cmax
• Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, AUC
• To evaluate Pharmacodynamics (PD) and other relevant blood tumor markers specific to tumor type
• To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30)
• Time to next therapy

Planned enrollment: 150 (estimated).

• HonorHealth, Scottsdale, Arizona
• START Los Angeles, Los Angeles, California
• Cedars-Sinai Medical Center, Los Angeles, California
• Valkyrie Clinical Trials (contact for more locations), Los Angeles, California
• BRCR - Coral Springs, Coral Springs, Florida
• BRCR - Tamarac, Tamarac, Florida
• Moffitt Cancer Center, Tampa, Florida
• Indiana University, Simon Comprehensive Cancer Center, Indianapolis, Indiana
• START Midwest, Grand Rapids, Michigan
• Washington University, St Louis, Missouri
• START New Jersey, East Brunswick, New Jersey
• Perlmutter Cancer Center at NYU Langone Health (contact for more locations), New York, New York
• University of North Carolina, Chapel Hill, North Carolina
• Case Western, University Hospitals Cleveland Medical Center, Cleveland, Ohio
• Sarah Cannon Research Institute Oncology Partners, Nashville, Tennessee
• START Dallas Fort Worth, Fort Worth, Texas
• The University of Texas MD Anderson Cancer Center, Houston, Texas
• Huntsman Cancer Institute - University of Utah, Salt Lake City, Utah
• START Mountain Region, West Valley City, Utah
• UVA Comprehensive Cancer Center, Charlottesville, Virginia
• Virginia Cancer Specialists, Fairfax, Virginia
• Virginia Mason Medical Center, Seattle, Washington
• University of Wisconsin, Madison, Wisconsin

7 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07659795

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 25, 2026. Public record; not medical advice.