A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Colorectal Cancer
TARGET-D 203
A Phase 2, 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)
2 other identifiers
interventional
150
2 countries
8
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 colorectal-cancer
Started Jul 2026
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 15, 2026
CompletedFirst Posted
Study publicly available on registry
June 22, 2026
CompletedStudy Start
First participant enrolled
July 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
July 27, 2026
July 1, 2026
11 months
June 15, 2026
July 23, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Confirmed ORR by blinded independent central review (BICR) per RESIST v1.1 - 2L CRC only
Overall Response Rate per RECIST version 1.1, per blinded independent central review (BICR)
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
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations
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
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations
6 months
Secondary Outcomes (6)
Confirmed ORR per RECIST v1.1 assessed by BICR (primary) and Investigator (secondary) assessments
24 months
Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, Cmax
20 weeks
Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, AUC
20 weeks
To evaluate Pharmacodynamics (PD) and other relevant blood tumor markers specific to tumor type
Up to 2.5 years
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)
24 months
- +1 more secondary outcomes
Other Outcomes (1)
Imaging of tumor metabolism changes in 2L monotherapy patients
24 months
Study Arms (3)
VS-7375 Monotherapy or Preferred Combination in 2L+ CRC
EXPERIMENTALParticipants randomized to a treatment in 2:1 ratio
VS-7375 with chosen regimen in 2L+ CRC
EXPERIMENTALVS-7375 + cetuximab and mFOLFOX in 1L CRC
EXPERIMENTALInterventions
Intravenous infusion
Intravenous infusion
Taken by mouth
Eligibility Criteria
You may qualify 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
- L+ 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.
- L patients:
- Treatment-naïve or received no more than 1 cycle of standard systemic therapy for metastatic disease.
You may not qualify 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Verastem, Inc.lead
Study Sites (8)
START Los Angeles
Los Angeles, California, 90025, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
START Midwest
Grand Rapids, Michigan, 49546, United States
START New Jersey
East Brunswick, New Jersey, 08816, United States
START Dallas Fort Worth
Fort Worth, Texas, 76104, United States
START Mountain Region
West Valley City, Utah, 84119, United States
Icon Cancer Centre South Brisbane
South Brisbane, Queensland, 4101, Australia
Icon Cancer Centre Adelaide
Kurralta Park, South Australia, 5037, Australia
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 15, 2026
First Posted
June 22, 2026
Study Start
July 1, 2026
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
December 1, 2028
Last Updated
July 27, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share