A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer (TARGET-D 202)

November 5, 2026 updated by: Verastem, Inc.

A Phase 2, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Patients With Previously Treated, Advanced KRAS G12D-Mutated Non-Small Cell Lung Cancer (TARGET-D 202)

This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab in patients with metastatic KRAS G12D - mutated Non-Small Cell Lung Cancer

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

105

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
      • Camperdown, New South Wales, Australia, 2050
        • Recruiting
        • Chris O'Brien Lifehouse
        • Principal Investigator:
          • Malinda Itchins, MD
        • Contact:
      • Sydney, New South Wales, Australia, 2109
        • Recruiting
        • Macquarie University Hospital
        • Principal Investigator:
          • John Park, MD
        • Contact:
    • Queensland
      • Brisbane, Queensland, Australia, 4101
        • Recruiting
        • ICON Cancer Centre South Brisbane
        • Contact:
        • Principal Investigator:
          • Jermaine Coward, MD
  • Puerto Rico
      • San Juan, Puerto Rico, 00907
        • Recruiting
        • BRCR Global- San Juan
        • Contact:
        • Principal Investigator:
          • Alexandra Deya, MD
      • Yauco, Puerto Rico, 00698
        • Recruiting
        • BRCR Global- Yauco
        • Contact:
        • Principal Investigator:
          • Maryknoll De La Paz, Md
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • HonorHealth Research Institute
        • Principal Investigator:
          • Frank Tsai, MD
        • Contact:
    • California
      • Los Angeles, California, United States, 90048
      • Los Angeles, California, United States, 90067
        • Recruiting
        • Valkyrie Clinical Trials
        • Principal Investigator:
          • David Berz, MD
        • Contact:
      • Los Angeles, California, United States, 90025
        • Recruiting
        • START LA
        • Principal Investigator:
          • Navid Hafez, MD
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Cancer Center
        • Principal Investigator:
          • Tejas Patil, MD
        • Contact:
    • Florida
      • Coral Springs, Florida, United States, 33065
        • Recruiting
        • BRCR Global - Coral Springs
        • Principal Investigator:
          • Sumit Sawhney, MD
        • Contact:
      • Tamarac, Florida, United States, 33321
        • Recruiting
        • BRCR Global- Tamarac
        • Contact:
        • Principal Investigator:
          • Andrew Schneider, MD
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffit Cancer Centre
        • Principal Investigator:
          • Andreas Saltos, MD
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory Winship Cancer Institute
        • Principal Investigator:
          • Jennifer Carlisle, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Kathryn Arbour, MD
        • Contact:
      • New York, New York, United States, 10016
        • Recruiting
        • NYU
        • Principal Investigator:
          • Rajwanth Veluswamy, MD
        • Contact:
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina at Chapel Hill
        • Principal Investigator:
          • Shetal Patel, MD, PhD
        • Contact:
        • Contact:
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Recruiting
        • START Fort Worth
        • Principal Investigator:
          • Salwan Almutar, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Marcelo Negrao, MD
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah
        • Contact:
        • Principal Investigator:
          • Matthew Gumbleton, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia
        • Principal Investigator:
          • Richard Hall, MD
        • Contact:
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
        • Principal Investigator:
          • Alexander Spira, MD
        • Contact:

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histopathology confirmed unresectable locally advanced or metastatic NSCLC
  • Measurable disease per RECIST 1.1
  • Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing)
  • ECOG PS=0 or 1
  • Adequate organ function
  • Received prior treatment with a platinum-based chemotherapy regimen and an immune checkpoint inhibitor in the advanced, non-resectable setting.
  • Have documented disease progression during or following their most recent prior line of therapy.

Patients with 2L/3L on stable or preferred dose:

  • Received at least 1 and no more than 2 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC.

Patients with 2L-4L with brain metastases:

  • Received at least 1 and no more than 3 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC.
  • Have asymptomatic and untreated brain metastases
  • At least 1 untreated measurable brain lesion per mRECIST v1.1 with a long axis ≥ 0.5 cm and ≤ 3 cm.

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
  • History of drug-induced Interstitial Lung Disease
  • Receipt of prior direct RAS inhibitor
  • 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 2L/3L

2L/3L VS-7375 dose
Drug: VS-7375

Taken by mouth
Experimental: VS-7375 Monotherapy 2L/3L Preferred Dose

2L/3L Preferred VS-7375 dose
Drug: VS-7375

Taken by mouth
Experimental: 2L-4L with brain metastasis

2L-4L VS-7375 dose
Drug: VS-7375

Taken by mouth

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
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 administered on a daily oral schedule in participants with KRAS G12D-mutated NSCLC
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
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 administered on a daily oral schedule in participants with KRAS G12D-mutated NSCLC
24 months
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
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 non-small cell lung 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
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 22, 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)

November 6, 2026

Last Update Submitted That Met QC Criteria

November 5, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VS-7375-202
  • 2026-526472-23-00 (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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