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Phase 2 Study of Oral VS-7375 in Adults with Advanced KRAS G12D‑Mutated Non‑Small Cell Lung Cancer Previously Treated

Verified siteFast replyInvestigationalNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on Non-Small Cell Lung Cancer that carries a specific genetic change called KRAS G12D. Participants receive the experimental medicine VS-7375, which is taken as a tablet by mouth each day. The goal of the research is to see how well this drug can shrink or stop the growth of the cancer while also checking that it is safe for patients who have already received other treatments.

Enrolled individuals will start the daily tablet regimen and attend regular clinic visits where doctors will monitor health, record any side effects, and perform imaging scans to look at the tumor and any brain spots that may be present. The study continues as long as the medication appears to work and is tolerated, with the possibility of stopping the drug if significant problems arise or if the disease progresses.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Baseline Assessments

    After you join the study, you will undergo a series of initial examinations. These include physical measurements, blood tests, and imaging scans such as CT or MRI to document the size and location of your tumor. The purpose is to confirm that you have Non‑Small Cell Lung Cancer with a KRAS G12D mutation and to record your baseline health status before starting treatment.

  2. Step 2

    Start of Study Medication

    You will begin taking the investigational drug VS‑7375. Each tablet contains 1200 mg of the active substance and is taken by mouth once daily. The medication is intended to be taken every day for as long as you remain in the study, unless the study team decides to stop or modify the treatment.

  3. Step 3

    Daily Medication Intake

    You will continue to swallow one VS‑7375 tablet each day, preferably at the same time each day, as directed by the study team. No additional dosing adjustments are required unless you experience side effects that need medical attention.

  4. Step 4

    Safety Monitoring Visits

    At regular clinic visits, the study team will check for any side effects or adverse events. This includes asking about symptoms, measuring vital signs, and performing blood tests. All observed side effects, including serious adverse events, will be recorded in the study database.

  5. Step 5

    Tumor Response Assessments

    Periodically, you will undergo imaging studies to evaluate how your tumor is responding to the medication. The tumor size will be measured using the RECIST v1.1 criteria, which is a standardized method for assessing changes in tumor dimensions. If you have untreated brain metastases, additional brain imaging will be performed and evaluated using the modified RECIST (mRECIST) or RANO‑BM criteria.

  6. Step 6

    Dose Adjustments if Needed

    If the safety monitoring identifies significant side effects, the study protocol allows for temporary interruption of the medication or a reduction in the daily dose. Any such changes will be decided by the study physicians and will be documented in your study records.

  7. Step 7

    End of Treatment

    Treatment with VS‑7375 will end if the disease progresses, if you experience unacceptable toxicity, or if the study reaches its planned conclusion. At the time of discontinuation, a final set of safety assessments and imaging studies will be performed.

  8. Step 8

    Post‑Treatment Follow‑Up

    After stopping the medication, you will continue to attend follow‑up visits. These visits are intended to collect information on overall survival and any late‑appearing side effects. The follow‑up period continues until the study ends or until the investigators determine that no further data collection is required.

Who can join the trial?

17 criteria

  • Be at least 18 years old.
  • Have a diagnosis of unresectable locally advanced or metastatic non‑small cell lung cancer (NSCLC) confirmed by a tissue examination.
  • Show tumor that can be measured on scans, using the standard criteria called RECIST v1.1; the required imaging must be done within the 28 days before starting the study drug.
  • Have a known KRAS G12D mutation. This genetic change must be identified by a laboratory test such as next‑generation sequencing (NGS) or polymerase chain reaction (PCR) using a fresh biopsy when possible, or from stored tissue or a blood sample if a fresh biopsy cannot be done.
  • Have an ECOG performance status of 0 or 1, meaning you are fully active (0) or able to carry out light work (1) without being bedridden.
  • Previously received both a platinum‑based chemotherapy (a common type of cancer drug) and an immune checkpoint inhibitor (a medicine that helps the immune system attack cancer) for advanced disease.
  • Your cancer must have gotten worse during or after the most recent treatment you received.
  • If you are in study Part A or B, you must have had 1 to 2 prior lines of systemic therapy for advanced disease (systemic therapy means medicines that travel through the whole body). Any earlier chemotherapy given before surgery (adjuvant) or before other treatment (neoadjuvant) counts if the cancer grew back during treatment or within 6 months after finishing it.
  • If you are in study Part C, you must have had 1 to 3 prior lines of systemic therapy for advanced disease, with the same rules for counting earlier treatments.
  • If you are in study Part C, you must have asymptomatic and untreated brain metastases (cancer that has spread to the brain but is not causing symptoms and has not been treated).
  • If you are in study Part C, you must have at least one measurable brain lesion that is at least 0.5 cm and no larger than 3 cm, measured by the criteria called mRECIST v1.1.
  • Your laboratory tests must show adequate organ function, meaning your liver, kidneys, blood counts, and other organs are working well enough to handle the study drug.
  • You must have recovered from any side effects of previous treatments to a mild level (grade ≤ 1), except for hair loss or mild nerve problems. Hormone‑related side effects up to grade 2 that need medication are allowed.
  • Female participants must either:
    • Not be able to become pregnant (for example, due to surgery or being post‑menopausal), or
    • If they could become pregnant, have a negative pregnancy test, agree not to try to become pregnant, and use two forms of highly effective birth control (or one form plus a barrier method) during the study and for at least 6 months after the last dose.
    • Male participants must agree not to donate sperm and, if they have a partner who could become pregnant, must use a condom in addition to the partner using a highly effective birth control method for at least 100 days after the last dose.
    • Be willing to sign an informed consent form, showing that you understand the study and agree to follow its procedures.

Who cannot join the trial?

25 criteria

  • Having a tumor that contains other common RAS mutations besides the KRAS G12D change.
  • Having a tumor with any other treatable mutation such as EGFR, HER2, BRAF, MET (exon 14 skipping), ALK, ROS‑1, RET or NTRK.
  • Having been treated before with a drug that directly blocks RAS proteins.
  • Having a history or current diagnosis of interstitial lung disease (a scar‑like lung condition) or pneumonitis that needed steroid medication, or having had drug‑induced lung inflammation.
  • Having had major surgery (other than a simple diagnostic test) within the 4 weeks before the study start, or planning a major operation during the study.
  • Having received chemotherapy, targeted cancer therapy, or radiation (except palliative radiation) within 4 weeks (or five drug half‑lives) before the first study dose, or having received immunotherapy within 4 weeks. Radiation to the lung or brain needs a longer waiting period.
  • Having taken more than one experimental cancer treatment for advanced or metastatic lung cancer.
  • Having taken any other investigational drug within 4 weeks (or five half‑lives) before the first dose, or currently being enrolled in another interventional study.
  • Using strong CYP3A4 enzyme inhibitors or inducers, or other medicines that interact closely with the study drug, within 14 days (or three half‑lives) before the first dose. This also includes drinking grapefruit or grapefruit juice during the week before the study.
  • Using proton pump inhibitors (medicines that reduce stomach acid) within 5 days before the first dose, or using H2 receptor antagonists (another type of acid‑reducing drug) within 1 day before the first dose.
  • Being unable to swallow pills, or having gastrointestinal problems (such as major stomach surgery) that could prevent the medication from being absorbed.
  • Needing supplemental oxygen to keep resting oxygen levels at or above 90%.
  • Having a known infection with hepatitis B, hepatitis C, or HIV (unless HIV is well‑controlled with a stable low viral load and a healthy white‑blood‑cell count).
  • Having received an allogeneic tissue, solid‑organ, or bone‑marrow transplant.
  • Having current symptomatic heart failure, severe heart disease (New York Heart Association class III or IV), a heart attack within the past 3 months, unstable heart rhythm, unstable chest pain, or severe obstructive lung disease.
  • Having uncontrolled serious disease of the blood, kidneys, liver, hormones, lungs, digestive system, heart, mind, clotting, nerves, skin, autoimmune system, or severe drug allergies that could raise the risk of side effects.
  • Having an uncontrolled illness such as an active infection that needs treatment, ongoing drug abuse, or a social situation that would make it difficult to follow study requirements.
  • Having another cancer that is not cured, unless it was treated with curative intent and has been disease‑free for at least 3 years (certain low‑risk cancers are allowed).
  • Being pregnant or breastfeeding.
  • Having a known allergy or hypersensitivity to the study drug or any of its inactive ingredients.
  • For the early parts of the study (Parts A and B): having untreated or symptomatic brain (central nervous system) metastases.
  • For Part C only: having symptomatic brain metastases or untreated brain lesions larger than 3 cm.
  • For Part C only: needing more than 4 mg of dexamethasone (or equivalent) daily for at least 2 weeks before the first dose.
  • For Part C only: having radiographic evidence of leptomeningeal disease (cancer spread to the lining of the brain or spinal cord).
  • For Part C only: having a condition that makes magnetic resonance imaging (MRI) unsafe, such as certain implanted metal devices.
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Investigated drugs

VS-7375 is an experimental oral tablet that works by blocking a specific genetic change called KRAS G12D, which can help cancer cells grow. In this study, participants with advanced non‑small cell lung cancer that carries the KRAS G12D mutation take the medicine each day by mouth. The drug is being tested to see how well it can shrink or stop tumor growth and to learn about any side effects it may cause. It is given to patients who have already received one or two previous treatments for their cancer, or who have untreated brain spots that are not causing symptoms, after they have had up to three prior therapies.

What is already known about the treatment

VS-7375 - VS-7375 is taken as a tablet by mouth, usually 1200 mg once daily. It is still an investigational drug being studied in Phase 2 trials and is not yet approved for general medical use. The medicine is designed to treat advanced non‑small cell lung cancer that carries a KRAS G12D mutation. It works by blocking the abnormal KRAS protein, stopping the signal that makes cancer cells grow, and is classified as a KRAS‑targeted oral inhibitor.

Investigated diseases

KRAS G12D‑mutated Non‑Small Cell Lung Cancer - Non‑Small Cell Lung Cancer is a group of lung cancers that arise from the larger airway cells and grow more slowly than small cell types. The KRAS G12D mutation drives the cancer cells to divide rapidly and resist normal growth controls. Tumors often start in the lung and can enlarge to block airways or spread to nearby lymph nodes, making surgical removal difficult. As the disease advances, cancer cells may travel through the bloodstream to distant organs such as the brain, bones, or liver, forming new growths. Patients may experience worsening respiratory symptoms as the tumor expands and spreads.
Trial detailsLast updated 29 Oct 2026
Age18+ yearsPhasePhase IITrial ID2026-526472-23-00Protocol codeVS-7375-202Estimated enrolment81 patientsSponsorVerastem Inc.

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