A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors

NCT ID: NCT07020221

Last Updated: 2026-01-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

295 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-24

Study Completion Date

2028-12-31

Brief Summary

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This study will assess the safety and efficacy of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation.

Detailed Description

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Conditions

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Pancreatic Ductal Adenocarcinoma Non Small Cell Lung Cancer Colorectal Cancer Solid Tumor, Adult G12D Mutated KRAS

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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VS-7375 Dose Escalation

To determine the recommended phase 2 dose (RP2D) for VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Cetuximab + VS-7375 Dose Escalation

To determine the recommended phase 2 dose (RP2D) for cetuximab + VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Cetuximab

Intervention Type DRUG

Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).

VS-7375 Recommended Phase 2 Dose Expansion

To determine the efficacy of VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced PDAC, NSCLC, or solid tumors harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Cetuximab + VS-7375 Recommended Phase 2 Dose Expansion

To determine the efficacy of cetuximab +VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced CRC harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Cetuximab

Intervention Type DRUG

Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).

VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Escalation

To determine the recommended phase 2 dose (RP2D) for VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab in patients with advanced 1L NSCLC harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Carboplatin + Pemetrexed + Pembrolizumab

Intervention Type DRUG

A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer.

VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Expansion

To determine the efficacy of VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab at the RP2D in patients with advanced 1L NSCLC harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Carboplatin + Pemetrexed + Pembrolizumab

Intervention Type DRUG

A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer.

VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Escalation

To determine the recommended phase 2 dose (RP2D) for VS-7375 in combination with gemcitabine/nab-paclitaxel in patients with advanced PDAC harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Gemcitabine + Nab-paclitaxel

Intervention Type DRUG

A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma.

VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Expansion

To determine the efficacy of VS-7375 in combination with gemcitabine/nab-paclitaxel at the RP2D in patients with advanced PDAC harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Gemcitabine + Nab-paclitaxel

Intervention Type DRUG

A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma.

VS-7375 + Gemcitabine Dose Escalation

To determine the RP2D for VS-7375 in combination with gemcitabine in patients 75 years or older with advanced PDAC harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Gemcitabine

Intervention Type DRUG

A chemotherapy used for the treatment of several types of cancer including advanced or metastatic pancreatic ductal adenocarcinoma.

VS-7375 + Gemcitabine Dose Expansion

The determine the efficacy of VS-7375 in combination with gemcitabine at the RP2D in patients 75 years or older with advanced PDAC harboring a KRAS G12D mutation.

Group Type EXPERIMENTAL

VS-7375

Intervention Type DRUG

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Gemcitabine

Intervention Type DRUG

A chemotherapy used for the treatment of several types of cancer including advanced or metastatic pancreatic ductal adenocarcinoma.

Interventions

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VS-7375

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

Intervention Type DRUG

Cetuximab

Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).

Intervention Type DRUG

Carboplatin + Pemetrexed + Pembrolizumab

A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer.

Intervention Type DRUG

Gemcitabine

A chemotherapy used for the treatment of several types of cancer including advanced or metastatic pancreatic ductal adenocarcinoma.

Intervention Type DRUG

Gemcitabine + Nab-paclitaxel

A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma.

Intervention Type DRUG

Other Intervention Names

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Erbitux

Eligibility Criteria

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Inclusion Criteria

* Individuals ≥18 years of age.
* Agreement to sign and date an informed consent form (ICF) approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
* Histologic or cytologic evidence of locally advanced unresectable or metastatic solid tumor harboring a KRAS G12D mutation.
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate organ function
* Adequate cardiac function
* Recovered from all AEs due to previous therapies to Grade ≤1 or baseline.
* Agreement to use highly effective contraception

Exclusion Criteria

* Underwent major surgical procedure as defined by the Investigator, other than for diagnosis, within 4 weeks prior to Cycle 1 Day 1,
* Receipt of chemotherapy, targeted therapy, or radiotherapy (excluding palliative radiation) within 4 weeks or 5 half-lives, whichever is shorter, or immunotherapy within 4 weeks prior to Cycle 1 Day 1
* Treatment with any investigational drug at least 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.
* History of treatment with direct and specific KRAS G12D inhibitors.
* Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
* Inability to swallow oral medications.
* Evidence or history of uncontrolled, clinically significant hematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation, neurologic, dermatologic, autoimmune, or allergic disease
* Individuals who are pregnant or breastfeeding.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Verastem, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Laura & Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status RECRUITING

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Verastem Call Center

Role: CONTACT

1 781 292 4204

Facility Contacts

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Shannon Cyhan

Role: primary

Nilofer Azad

Role: primary

410-614-9169

Leon Pappas, MD

Role: primary

617-724-4000

Vaibhav Sahai, MD

Role: primary

800-865-1125

Sara Mitchum

Role: primary

314-273-8602

Jennifer Coffey

Role: primary

SCRI Referral Team

Role: primary

615-341-7844

Ly M Nguyen

Role: primary

832-794-3672

Laura Haug

Role: primary

801-213-5720

Colleen Soleau

Role: primary

206-287-6272

Other Identifiers

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VS-7375-101

Identifier Type: -

Identifier Source: org_study_id

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