NCT07020221 · Verastem, Inc.
A Phase 1/2a Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors
What this study is about
This study will assess the safety and effectiveness of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation.
View original scientific description
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.
Interventions
DRUG
VS-7375
VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.
DRUG
Cetuximab
Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).
DRUG
Carboplatin + Pemetrexed + Pembrolizumab
A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer.
DRUG
Gemcitabine
A chemotherapy used for the treatment of several types of cancer including advanced or metastatic pancreatic ductal adenocarcinoma.
DRUG
Gemcitabine + Nab-paclitaxel
A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma.
Primary outcome measures
Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375
Time frame: Up to 2.5 years
To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 administered on a daily oral schedule in participants with advanced solid tumors harboring a KRAS G12D mutation. Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, DLTs, and dose interruptions/reductions.
Part A: To identify the MTD or MFD
Time frame: Cycle 1 (each cycle is 21 days)
To identify the MTD or MFD using a BOIN design and recommend a dose for subsequent studies of VS-7375 on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor. Proportion/number of participants with DLTs during the DLT assessment period (through C1D21).
Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen
Time frame: Up to 2.5 years
To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen identified from Part A in participants with advanced KRAS G12D-mutated PDAC (cohort B1), NSCLC (cohort B2), and other solid tumors (cohort B3). Confirmed ORR, PFS rate, unconfirmed PR and CR rates, DCR, DOR, and PFS per RECIST v1.1. Overall Survival
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
To characterize the safety, tolerability, and AE profile of VS-7375 in the following combination regimens in participants with any solid tumor harboring a KRAS G12D mutation. * 2L+ therapy in combination with cetuximab in participants with any advanced or metastatic solid tumor harboring a KRAS G12D mutation * 1L therapy in combination with carboplatin, pembrolizumab, and pemetrexed in participants with previously untreated metastatic NSCLC * 2L+ therapy in combination with gemcitabine and nab-paclitaxel in participants with metastatic PDAC * 1L therapy in combination with gemcitabine in participants aged 75 years or older with previously untreated metastatic PDAC. Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, DLTs, and dose interruptions/reductions.
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)
To identify a recommended dose for subsequent studies of combination dosed VS-7375. Proportion/number of participants with DLTs during the DLT assessment period (through end of Cycle 1).
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
To determine the preliminary anticancer activity of the optimal regimen of VS-7375 as identified in Part C as: * 2L+ therapy in combination with cetuximab in participants with metastatic colorectal adenocarcinoma * 1L therapy in combination with carboplatin, pembrolizumab, and pemetrexed in participants with previously untreated metastatic NSCLC * 2L+ therapy in combination with gemcitabine and nab-paclitaxel in participants with metastatic PDAC * 1L therapy in combination with gemcitabine in participants aged 75 years or older with previously untreated metastatic PDAC. Confirmed ORR, PFS rate, unconfirmed PR and CR rates, DCR, DOR, and PFS per RECIST v1.1. Overall survival
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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.
- Must have received ≥1 prior line of standard systemic therapy for advanced or metastatic disease or experienced cancer progression within 6 months of neoadjuvant or adjuvant therapy.
- 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 t
Where
- Los Angeles, California
- Baltimore, Maryland
- Boston, Massachusetts
- Ann Arbor, Michigan
- St Louis, Missouri
- New York, New York
- Philadelphia, Pennsylvania
- Nashville, Tennessee
- Houston, Texas
- Salt Lake City, Utah
- Charlottesville, Virginia
- Fairfax, Virginia
And 1 more location — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 22, 2026 · Source of record for eligibility and locations