A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Colorectal Cancer (TARGET-D 203)

September 14, 2026 updated by: Verastem, Inc.

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)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Macquarie Park, New South Wales, Australia, 2109
        • Recruiting
        • Macquarie University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Andrew Parsonson, MBBS MMed (Clin Epi) FRACP
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Recruiting
        • ICON Cancer Centre South Brisbane
        • Contact:
        • Principal Investigator:
          • Jermaine Coward, MBBS, MRCP (UK), FRACP, PhD
    • South Australia
      • Kurralta Park, South Australia, Australia, 5037
        • Recruiting
        • Icon Cancer Centre Adelaide
        • Contact:
        • Principal Investigator:
          • Carolyn Bampton, MBBS, FRACP
  • United States
    • California
      • Los Angeles, California, United States, 90025
        • Recruiting
        • START Los Angeles
        • Contact:
        • Principal Investigator:
          • Navid Hafez, M.D., MPH
      • Los Angeles, California, United States, 90067
        • Recruiting
        • Valkyrie Clinical Trials (contact for more locations)
        • Principal Investigator:
          • David Berz, MD, PhD, MPH
        • Contact:
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Tiago Biachi de Castria, MD, PhD
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University, Simon Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Anita Turk, M.D.
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • START MidWest
        • Contact:
        • Principal Investigator:
          • Sreenivasa R Chandana, M.D., Ph.D.
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Principal Investigator:
          • Kian-Huat Lim, M.D., Ph.D.
        • Contact:
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Recruiting
        • START New Jersey
        • Contact:
        • Principal Investigator:
          • Bruno S Fang, M.D.
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute Oncology Partners
        • Principal Investigator:
          • Meredith Pelster, MD
        • Contact:
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Recruiting
        • START Dallas Fort Worth
        • Contact:
        • Principal Investigator:
          • Salwan Al Mutar, M.D., M.Sc.
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Principal Investigator:
          • Christine Parseghian, MD
        • Contact:
    • Utah
      • West Valley City, Utah, United States, 84119
        • Recruiting
        • START Mountain Region
        • Contact:
        • Principal Investigator:
          • José M Pacheco, M.D.
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • UVA Comprehensive Cancer Center
        • Principal Investigator:
          • Matthew Reilley, MD
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98101
        • Recruiting
        • Virginia Mason Medical Center
        • Contact:
        • Principal Investigator:
          • Jessica Lee, DO

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VS-7375 Monotherapy or Preferred Combination in 2L+ CRC
Participants randomized to a treatment in 2:1 ratio
Drug: panitumumab
Intravenous infusion
Drug: VS-7375
Taken by mouth
Drug: cetuximab
Intravenous infusion
Experimental: VS-7375 with chosen regimen in 2L+ CRC
Drug: panitumumab
Intravenous infusion
Drug: VS-7375
Taken by mouth
Drug: cetuximab
Intravenous infusion
Experimental: VS-7375 + cetuximab and mFOLFOX in 1L CRC
Drug: Cetuximab + mFOLFOX6
Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmed ORR by blinded independent central review (BICR) per RESIST v1.1 - 2L CRC only
Time Frame: 6 months
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
Time Frame: 6 months
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
Time Frame: 6 months
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, Cmax
Time Frame: 20 weeks
Maximum concentration (Cmax)
20 weeks
Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, AUC
Time Frame: 20 weeks
Area under plasma Concentration (AUC) 0 to t
20 weeks
To evaluate Pharmacodynamics (PD) and other relevant blood tumor markers specific to tumor type
Time Frame: Up to 2.5 years
CA19-9, CEA, CA-125
Up to 2.5 years
Confirmed ORR per RECIST v1.1 assessed by BICR (primary) and Investigator (secondary) assessments
Time Frame: 24 months
To evaluate additional efficacy parameters of VS-7375 monotherapy and VS-7375 in combination with cetuximab or panitumumab or cetuximab + mFOLFOX, administered on a daily oral schedule in participants with KRAS G12D-mutated CRC
24 months
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 Frame: 24 months
The EORTC QLQ-C30 is a validated questionnaire to assess the quality of life of colorectal cancer patients
24 months
Time to next therapy
Time Frame: 24 months
To assess the interval between initiation of study treatment and initiation of subsequent treatment
24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Imaging of tumor metabolism changes in 2L monotherapy patients
Time Frame: 24 months
To assess tumor metabolism dynamics on FDG-PET/CT
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Verastem, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

June 15, 2026

First Submitted That Met QC Criteria

June 15, 2026

First Posted (Actual)

June 22, 2026

Study Record Updates

Last Update Posted (Actual)

September 16, 2026

Last Update Submitted That Met QC Criteria

September 14, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VS-7375-203
  • 2026-526473-42-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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