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Safety and Preliminary Efficacy of Oral GSK5460025A Alone or with Drug Combination in Adult Patients with dMMR/MSI‑H Colorectal Cancer

Fast replyInvestigationalNo placebo
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What is this trial about?

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

This trial involves adults with cancers that have a specific genetic feature called Mismatch Repair-deficient (dMMR) or Microsatellite Instability-High (MSI-H). These features are found in solid tumors such as colorectal cancer and endometrial cancer. The investigational medicine is an oral capsule known as GSK5460025, which may be given alone (monotherapy) or together with other anti-cancer agents. The study is a phase 1/2 open-label trial, meaning that the treatment and its effects are observed directly.

The main goal is to determine whether the medicine can be given safely, to identify the appropriate dose, and to see early signs that it may shrink or control the tumors.

Participants will take the capsule by mouth on a regular schedule. In the first part of the trial, the dose is adjusted to find the level that is tolerated without serious side effects. In the second part, patients with colorectal cancer or endometrial cancer receive the selected dose and are monitored with routine visits, blood tests, and imaging scans to check for tumor response and any side effects.

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

    First dose of study medication

    You receive the oral capsule containing gsk5460025 and take it by mouth as instructed by the study staff.

    The specific amount of medicine and how often it should be taken are provided to you in the study instructions; these details are not listed in the summary.

  2. Step 2

    Regular intake of the medication

    You continue to take the gsk5460025 capsule according to the schedule given by the study team.

    The exact frequency (for example, daily) and the length of time you will stay on the medication are explained to you at the start of treatment.

  3. Step 3

    Initial safety observation period

    During the early part of the study, special attention is paid to any dose limiting toxicities (dlt), which are side effects that may be serious enough to stop increasing the dose.

    You may have additional visits or contacts with the study team to report any new symptoms.

  4. Step 4

    Routine safety assessments

    You attend scheduled visits where blood samples are taken to measure the amount of gsk5460025 in your blood and to check other laboratory values.

    Electrocardiograms (ecgs) and vital‑sign checks (such as blood pressure and heart rate) are performed to monitor your overall health.

    Any adverse events, including serious ones, are recorded and evaluated for severity.

  5. Step 5

    Tumor response evaluation

    Imaging studies are performed at predefined times to assess the size of the tumor according to the response evaluation criteria in solid tumors (recist 1.1) guidelines.

    The results help determine whether there is a complete response, partial response, or no change, which contributes to the study’s objective response rate.

  6. Step 6

    Ongoing monitoring for adverse events

    Throughout the study you continue to report any treatment‑emergent adverse events (teaes) and treatment‑emergent serious adverse events (tesaes).

    The study team assesses each event and may adjust the dose of gsk5460025 if needed.

  7. Step 7

    Decision points for dose modification

    If an adverse event is judged to be related to the medication and meets predefined criteria, the dose may be reduced, paused, or stopped according to the protocol.

    These decisions are made by the investigators based on the safety data you provide.

  8. Step 8

    Continuation until disease progression or study end

    You remain on the medication and continue regular assessments until the cancer shows progression, unacceptable toxicity occurs, or the study reaches its planned conclusion.

    The time from the first dose to disease progression is recorded as progression‑free survival.

Who can join the trial?

12 criteria

  • Participant must be at least 18 years old.
  • For the part of the study that looks at treatment effect, the participant must have a histologically diagnosed (diagnosed by examining tissue under a microscope) advanced colorectal cancer or endometrial cancer. Advanced means the cancer cannot be removed by surgery (unresectable), has spread to other parts of the body (metastatic), or has come back after treatment (recurrent).
  • The participant must have already received at least 1 but no more than 3 lines (different rounds) of systemic anticancer therapy for their advanced disease, and one of those treatments must have been an immune checkpoint inhibitor (a type of medicine that helps the immune system attack cancer).
  • The participant must have measurable disease, meaning at least one tumor that can be measured, as assessed during the screening period using the RECIST 1.1 criteria (a standard way doctors track tumor size).
  • Participant must have a histologically diagnosed advanced solid tumor (cancer that forms a solid mass) that cannot be removed by surgery, has spread, or has returned.
  • Participant must have a known dMMR/MSI‑H status (specific genetic features of the tumor) determined by a certified laboratory, or if this status is unknown, it will be tested by a central reference laboratory.
  • Participant must be able to provide a tissue sample, either an archived sample or a fresh sample (preferred), that is preserved as formalin‑fixed, paraffin‑embedded (FFPE) tissue.
  • Participant must plan to receive the study drug GSK5460025 as their next cancer treatment.
  • Participant must have an ECOG performance status of 0‑2 (a scale that measures daily activity ability, where 0 is fully active and 2 means able to care for self but unable to work).
  • Participant must be expected to live at least 3 more months based on the doctor’s judgment.
  • Participant must have adequate organ function (the heart, liver, kidneys, and blood‑forming organs work well enough) as defined in the study protocol.
  • For the safety‑focused part of the study (Part 1), the participant must have an advanced solid tumor that has exhausted all standard treatment options.

Who cannot join the trial?

8 criteria

  • You have not fully healed (to mild side‑effects or back to how you were before) from problems that occurred after earlier cancer treatments; this means you still have significant Adverse Events from those therapies.
  • You have previously taken a Werner (WRN) inhibitor or a Nucleotide Excision Repair Targeting (NERT) agent, which are special types of experimental drugs.
  • You are unable to swallow the study pills or keep them in your mouth long enough for them to work.
  • You have cancer that has spread to the brain or the central nervous system (CNS), or these brain spots have gotten worse and have not been treated.
  • You have another cancer that got worse or needed active treatment within the past two years, because this could make it hard to judge the study’s effect; an exception is made for certain skin cancers (like basal or squamous cell carcinoma) or very early‑stage cancers (called in situ carcinomas) that were removed and have not spread.
  • You have a stomach or intestinal problem that could change how well the study medicine is absorbed, such as severe diarrhea, blockage, or other serious gastrointestinal disease.
  • You have severe liver scarring (cirrhosis) or an unstable liver or bile duct condition (called biliary disease).
  • You are known to be allergic (hypersensitive) to any part of the study drug or its inactive ingredients (known as excipients).
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Investigated drugs

GSK5460025A is an experimental oral capsule being studied as a new cancer treatment. In this trial, participants take the capsule by mouth to see if it is safe, how well it is tolerated, and what dose works best. The study looks at the drug alone and also how it works when combined with other cancer medicines. Researchers are especially interested in whether the drug can shrink or control tumors in people who have certain types of solid tumors that have a mismatch repair deficiency or high microsatellite instability, such as colorectal and endometrial cancers.

What is already known about the treatment

GSK5460025A - GSK5460025A is taken as an oral capsule, so patients swallow a pill. It is an investigational drug that is currently being studied in Phase 1/2 trials and is not yet approved for routine medical use. The trial is testing it for colorectal cancer with mismatch‑repair deficiency or high microsatellite instability. The medicine works by blocking a specific protein that helps cancer cells repair their DNA, which slows tumor growth, and it is classified as a small‑molecule inhibitor of DNA‑repair pathways.

Investigated diseases

  • Colorectal cancer

    Colorectal cancer is a cancer that begins in the colon or rectum, which are parts of the large intestine. It often starts as a small growth called a polyp that can turn into cancer over time. As the tumor grows, it can invade the wall of the bowel and spread to nearby tissues. Later it may travel through the bloodstream to other parts of the body. Symptoms can include changes in bowel habits, blood in the stool, and abdominal discomfort.

  • Endometrial cancer

    Endometrial cancer is a cancer that starts in the lining of the uterus, known as the endometrium. It usually develops slowly from abnormal cells that become a tumor inside the uterus. As the tumor enlarges, it can spread through the wall of the uterus and reach nearby organs. It may also travel to distant sites through the bloodstream. Common early signs include unusual vaginal bleeding.

Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase I/IITrial ID2025-522318-21-00Protocol code224035Estimated enrolment47 patientsSponsorGlaxosmithkline Research & Development Limited

sourced from the EU Clinical Trials Register and site verification

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