Recruiting
Phase 1
Phase 2

VS-7375

Sponsor:

Verastem, Inc.

Code:

NCT07020221

Conditions

Pancreatic Ductal Adenocarcinoma

Non Small Cell Lung Cancer

Colorectal Cancer

Solid Tumor, Adult

G12D Mutated KRAS

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

VS-7375

Cetuximab

Carboplatin + Pemetrexed + Pembrolizumab

Gemcitabine + Nab-paclitaxel

Pembrolizumab

Study Details

Brief summary:

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.

Conditions

Pancreatic Ductal Adenocarcinoma

Non Small Cell Lung Cancer

Colorectal Cancer

Solid Tumor, Adult

G12D Mutated KRAS

Study ID

NCT07020221

Start date

Jun 24, 2025

Status verified date

Apr, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key 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

Key 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 RAS 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.

Study Design

Enrollment

616 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: VS-7375 Monotherapy Dose Escalation

To characterize the safety and tolerability of escalating doses of VS-7375 as monotherapy and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced solid tumors harboring KRAS G12D mutation.

experimental: VS-7375 Monotherapy Dose Expansion - PDAC

To evaluate the efficacy of VS-7375 at the recommended phase 2 dose (RP2Ds) in patients with metastatic PDAC harboring KRAS G12D-mutation.

experimental: VS-7375 Monotherapy Dose Expansion - NSCLC

To evaluate the efficacy of VS-7375 at the recommended phase 2 dose (RP2Ds) in patients with metastatic NSCLC harboring KRAS G12D-mutation.

experimental: VS-7375 Monotherapy Dose Expansion - Solid Tumors

To evaluate the efficacy of VS-7375 at the recommended phase 2 dose (RP2Ds) in patients with metastatic solid tumors harboring KRAS G12D-mutation.

experimental: VS-7375 + Cetuximab Dose Escalation

To characterize the safety and tolerability of escalating doses of VS-7375 in combination with cetuximab and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced or metastatic PDAC, BTC, CRC harboring KRAS G12D-mutation.

experimental: VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Escalation

To characterize the safety and tolerability of escalating doses of VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab and to determine the recommended phase 2 dose (RP2Ds) in patients with metastatic NSCLC harboring KRAS G12D-mutation.

experimental: VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Escalation

To characterize the safety and tolerability of escalating doses of VS-7375 in combination with gemcitabine/nab-paclitaxel and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced or metastatic PDAC harboring KRAS G12D-mutation.

experimental: VS-7375 + Pembrolizumab Dose Escalation

To characterize the safety and tolerability of escalating doses of VS-7375 in combination with pembrolizumab and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced or metastatic NSCLC harboring KRAS G12D-mutation.

experimental: VS-7375 + Defactinib Dose Escalation

To characterize the safety and tolerability of escalating doses of VS-7375 in combination with defactinib and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced or metastatic NSCLC harboring KRAS G12D-mutation.

experimental: VS-7375 + Cetuximab Dose Expansion

To evaluate the efficacy of VS-7375 in combination with cetuximab at the recommended phase 2 dose (RP2Ds) in patients with with advanced or metastatic CRC harboring KRAS G12D-mutation.

experimental: VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Expansion

To evaluate the efficacy of VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab at the recommended phase 2 dose (RP2Ds) in patients with metastatic NSCLC harboring KRAS G12D-mutation.

experimental: VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Expansion

To evaluate the efficacy of VS-7375 in combination with gemcitabine/nab-paclitaxel at the recommended phase 2 dose (RP2Ds) in patients with metastatic PDAC harboring KRAS G12D-mutation.

experimental: VS-7375 + Midazolam and Repaglinide Drug-Drug Interaction

To assess the drug-drug interaction of VS-7375 in combination with midazolam and repaglinide in patients with advanced or metastatic PDAC, NSCLC, and CRC harboring a KRAS G12D mutation.

experimental: VS-7375 Serial Biopsy

To characterize the preliminary anti-cancer activity of VS-7375 in participants with metastatic PDAC who have received 2 or 3 prior therapies, correlated with biopsy-obtained biomarkers.

Interventions

VS-7375

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

Cetuximab

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

Carboplatin + Pemetrexed + Pembrolizumab

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

Gemcitabine + Nab-paclitaxel

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

Pembrolizumab

Immunotherapy used as a first-line treatment for advanced non-squamous non-small cell lung cancer.

Defactinib

A potent, selective, reversible inhibitor of focal adhesion kinase that also inhibits proline-rich tyrosine kinase-2

Midazolam

A short-acting benzodiazepine CNS depressant that has sedative, anxiolytic, amnesic, and hypnotic effects.

Repaglinide

A rapid-acting insulin secretagogue used to lower postprandial blood glucose in patients with type 2 diabetes mellitus.

Primary outcome measure

  • Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 [ Time Frame: Up to 2.5 years ]
  • Part A: To identify the MTD or MFD [ Time Frame: Cycle 1 (each cycle is 21 days) ]
  • Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen [ Time Frame: Up to 2.5 years ]
  • Part C: To characterize the safety, tolerability, and AE profile of VS-7375 in combination regimens. [ Time Frame: From enrollment to the end of treatment; an average of 9 months ]
  • Part C: To identify a recommended dose for subsequent studies of combination dosed VS-7375. [ Time Frame: Cycle 1 (each cycle is 21 or 28 days) ]
  • Part D: To determine the preliminary anticancer activity of the optimal regimen of VS-7375 as identified in Part C [ Time Frame: Up to 2.5 years ]
  • Part E: To determine the impact of VS-7375 on the PK of midazolam or repaglinide [ Time Frame: Up to 2.5 years ]
  • Part E: To determine the impact of VS-7375 on the PK of midazolam or repaglinide [ Time Frame: 2.5 years ]
  • Part E: To characterize the safety, tolerability, and AE profile of VS-7375 administered in combination with CYP3A4 and CYP2C8 substrates [ Time Frame: 2.5 years ]
  • Part F: Serial biopsy [ Time Frame: Up to 2.5 years ]

Central Contacts and Locations

Central contacts

Verastem Call Center

1 781 292 4204clinicaltrials@verastem.com

Locations

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Contacts

Shannon Cyhan

shannon.cyhan@cshs.org

Principal Investigator:

Arsen Osipov, MD

Johns Hopkins University

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Nilofer Azad

410-614-3644nilo.azad@jhu.edu

Principal Investigator:

Nilofer Azad, MD

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Leon Pappas, MD

617-724-4000lpappas3@mgb.org

Principal Investigator:

Leon Pappas, MD

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Vaibhav Sahai, MD

800-865-1125CancerAnswerLine@med.umich.edu

Principal Investigator:

Vaibhav Sahai, MBBS, MS

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Sara Mitchum

314-273-8602saram@wustl.edu

Principal Investigator:

Kian-Huat Lim, MD

Laura & Isaac Perlmutter Cancer Center at NYU Langone

Recruiting

New York, New York, United States, 10016

Contacts

Jennifer Coffey

DL_Phase1Screening@nyulangone.org

Principal Investigator:

Kristen Spencer, DO

Univ of Pennsylvania, Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Mark O'Hara, MD

215-360-0919Mark.OHara@pennmedicine.upenn.edu

Principal Investigator:

Mark O'Hara, MD

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

SCRI Referral Team

615-341-7844SCRI.DDUreferrals@scri.com

Principal Investigator:

Melissa Johnson, MD

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Ly M Nguyen

832-794-3672lmnguyen1@mdanderson.org

Principal Investigator:

David Hong, MD

Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Susan Sharry

801-585-3453susan.sharry@hci.utah.edu

Principal Investigator:

Matthew Gumbleton, MD

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Polly Wu

434-924-9286rw6aq@uvahealth.org

Principal Investigator:

Matthew Reilley, MD

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Carrie Friedman, RN, BSN, OCN

703-636-1473carrie.friedman@usoncology.com

Principal Investigator:

Alexander Spira, MD

Virginia Mason Medical Center

Recruiting

Seattle, Washington, United States, 98101

Contacts

Priscilla Kim

206-287-6277priscilla.kim902@commonspirit.org

Principal Investigator:

Vincent Picozzi, MD

More Information

Sponsor

Verastem, Inc.

Last update posted

Oct 15, 2026

Last verified

Apr, 2026

Keywords

  • KRAS G12D mutation
  • Solid tumors
  • Non Small Cell Lung Cancer
  • Lung Cancer
  • Colorectal Cancer
  • Metastatic Cancer
  • Pancreatic Cancer
  • Pancreatic Ductal Adenocarcinoma
  • NSCLC
  • CRC
  • PDAC
  • Pancreatic Neoplasms
  • Colorectal Neoplasms
  • Lung Neoplasms
  • Gastrointestinal Neoplasms
  • KRAS
  • RAS
  • Biliary Tract Cancer
  • BTC
  • Biliary Tract Neoplasms
  • Intrahepatic cholangiocarcinoma
  • Appendiceal Cancer
  • Endometrial Cancer
  • Small bowel Cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Verastem, Inc. on 2026-10-15. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.