A Phase II, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, With and Without an Anti-EGFR Antibody, and With an Anti-EGFR Antibody and Chemotherapy, in Patients With Metastatic KRAS G12D-Mutated Colorectal Adenocarcinoma (TARGET-D 203)

Study Identifier:
VS-7375-203
CT.gov Identifier:
NCT07659795
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
2026-526473-42-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study Summary

This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab or panitumumab and cetuximab plus mFOLFOX in patients with metastatic KRAS G12D - mutated Colorectal Cancer

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Bowel (Colorectal)
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: EXPERIMENTAL: VS-7375 + cetuximab and mFOLFOX in 1L CRC
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Drug: Drug: Cetuximab + mFOLFOX6
Drug: Intravenous infusion
Drug: EXPERIMENTAL: VS-7375 Monotherapy or Preferred Combination in 2L+ CRC
Drug: Participants randomized to a treatment in 2: 1 ratio
Drug: Drug: cetuximab
Drug: Drug: panitumumab
Drug: Drug: VS-7375
Drug: Taken by mouth
Drug: EXPERIMENTAL: VS-7375 with chosen regimen in 2L+ CRC
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • * 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.

    KRAS G12D-mutated 2L+ metastatic CRC

    Advanced colorectal cancer
Exclusion criteria
  • 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

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Dallas Fort Worth
Fort Worth, TX, United States, 76104
Investigator
Salwan Al Mutar
Status
Will Be Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)
Location
START Los Angeles
Los Angeles, CA, United States, 90025
Investigator
Navid Hafez
Status
Will Be Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Sreenivasa Chandana
Status
Will Be Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)
Location
START Mountain Region
West Valley City, UT, United States, 84119
Investigator
Jose Pacheco
Status
Will Be Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)
Location
START New Jersey
East Brunswick, NJ, United States, 08816
Investigator
Bruno Fang
Status
Will Be Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)