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Study on the Safety and Effectiveness of Pembrolizumab and Tretinoin in Patients with PD-1 Refractory Melanoma

Verified siteRegistered drugNo placebo
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What is this trial about?

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

This clinical trial is focused on studying treatments for melanoma, a type of skin cancer. The study involves several investigational treatments, including pembrolizumab (also known as MK-3475), which is a medication that helps the immune system fight cancer. Other treatments being tested in combination with pembrolizumab include tretinoin, quavonlimab (MK-1308A), favezelimab (MK-4280A), lenvatinib (MK-7902), and vibostolimab (MK-7684). These treatments are being studied to see how safe and effective they are when used together or alone in people with melanoma that has not responded to previous treatments.

The purpose of this study is to assess the safety and effectiveness of these treatment combinations. Participants will receive the treatments either through capsules taken by mouth or through an infusion, which is a way of delivering medication directly into the bloodstream. The study will monitor participants for any side effects and measure how well the cancer responds to the treatments. The study will also evaluate how long any positive effects last.

Participants in this study have melanoma that is not treatable with surgery and have not received prior treatment for advanced stages of the disease. The study will continue over several years to gather comprehensive data on the safety and effectiveness of these treatments. The goal is to find new ways to help people with melanoma, especially those whose cancer has not responded to other treatments.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial assessment

    Upon joining the study, an initial assessment is conducted to confirm eligibility. This includes verifying a diagnosis of melanoma that cannot be treated with local therapy and ensuring no prior treatment for advanced disease.

    A tumor biopsy is required to proceed.

  2. Step 2

    Safety lead-in phase

    The safety lead-in phase aims to evaluate the safety and tolerability of the treatment combinations. This involves monitoring for any adverse effects.

    During this phase, the percentage of participants experiencing dose-limiting toxicity or adverse events is assessed.

  3. Step 3

    Treatment administration

    Participants receive treatments that may include pembrolizumab alone or in combination with investigational agents.

    Medications such as tretinoin (oral use), pembrolizumab (intravenous infusion), lenvatinib (oral use), and vibostolimab (intravenous infusion) are administered according to the study protocol.

  4. Step 4

    Monitoring and evaluation

    Participants are regularly monitored for adverse events and treatment efficacy. This includes evaluating the objective response rate using specific criteria.

    The duration of response is also assessed to determine the effectiveness of the treatment.

  5. Step 5

    Conclusion of participation

    The study is estimated to conclude by July 2030. Participants will be informed of their results and any further steps if applicable.

    Participants are required to continue using contraception for a specified period after the last dose of study intervention, depending on the medication received.

Who can join the trial?

8 criteria

  • The patient must have a type of skin cancer called melanoma that has been confirmed through specific tests.
  • The melanoma must be at a stage where it cannot be removed by surgery, specifically Stage III or Stage IV.
  • The patient should not have received treatment for advanced melanoma before.
  • The patient must provide a sample of their tumor for testing.
  • If the patient is a male capable of producing sperm, he must agree to either not engage in sexual intercourse or use birth control during the study and for a short period after the last dose of the study medication.
  • If the patient is a female, she must not be pregnant or breastfeeding. She must either not be of childbearing potential or use effective birth control during the study and for a specified time after the last dose of the study medication. The time varies depending on the medication used.
  • The patient must have organs that are functioning well enough to participate in the study.
  • The patient must have recovered from any side effects of previous treatments to a mild level, except for hair loss or mild nerve damage.

Who cannot join the trial?

10 criteria

  • Patients who have not been diagnosed with PD-1 refractory melanoma. This is a type of skin cancer that does not respond to certain treatments targeting the PD-1 protein.
  • Patients who are not within the specified age range for the study. The study is open to certain age groups only.
  • Patients who are not willing or able to follow the study procedures and requirements.
  • Patients who have other medical conditions that might interfere with the study treatment or outcomes.
  • Patients who are pregnant or breastfeeding, as the study may involve treatments that could affect the baby.
  • Patients who are participating in another clinical trial at the same time, which could affect the results of this study.
  • Patients who have had a recent major surgery or are recovering from a major illness.
  • Patients who have a history of severe allergic reactions to any of the study medications.
  • Patients who have an active infection that requires treatment.
  • Patients who have a history of drug or alcohol abuse that could interfere with the study.
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Investigated drugs

  • Pembrolizumab

    is a medication used in this trial to help the body's immune system fight melanoma, a type of skin cancer. It works by blocking a specific protein that can stop the immune system from attacking cancer cells, allowing the immune system to better target and destroy these cells.

  • Investigational Agents

    are new treatments being tested in this trial. These agents are not yet approved for general use and are being studied to see how well they work and how safe they are when used alone or in combination with pembrolizumab. The goal is to find new ways to treat melanoma more effectively.

What is already known about the treatment

Pembrolizumab – Pembrolizumab is administered as an intravenous infusion, typically given in a clinical setting under the supervision of healthcare professionals. It is currently well-established in medical literature as an immunotherapy used to treat various types of cancer, including melanoma. The main therapeutic indication for pembrolizumab in this trial is for patients with PD-1 refractory melanoma. At the molecular level, pembrolizumab works by blocking the PD-1 pathway, which helps the immune system recognize and attack cancer cells more effectively. It is classified as a monoclonal antibody and is part of the broader category of immune checkpoint inhibitors.

Investigated diseases

PD-1 Refractory Melanoma – This is a type of skin cancer that does not respond to treatments targeting the PD-1 protein, which is involved in regulating the immune system. Melanoma begins in the melanocytes, the cells responsible for producing the pigment melanin, which gives skin its color. In its refractory form, the cancer persists despite attempts to block PD-1, a checkpoint protein on immune cells that normally helps keep the body's immune responses in check. The disease can spread to other parts of the body, making it more challenging to manage. It often requires alternative therapeutic strategies due to its resistance to standard PD-1 inhibitors. The progression of the disease can vary, with some cases advancing more rapidly than others.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase ITrial ID2023-506313-21-00Protocol codeMK-3475-02BEstimated enrolment189 patientsSponsorMerck Sharp & Dohme LLC

sourced from the EU Clinical Trials Register and site verification

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