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A Study of Valemetostat Tosylate in Adult Patients with Advanced Solid Tumors That Have Specific Gene Changes or Are Clear Cell Endometrial or Ovarian Cancers

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What is this trial about?

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

This study is looking at a treatment for certain types of advanced solid tumors, which are cancers that have spread or come back after previous treatment. The study focuses on tumors that have specific changes in genes involved in a process called chromatin remodeling, which affects how cells control their growth. These gene changes include problems in SMARCB1, SMARCA4, SMARCA2, SMARCC1, SMARCC2, ARID1A, ARID1B, PBRM1, BAP1, and other related genes. The study also includes patients with clear cell endometrial cancer or clear cell ovarian cancer that do not have these specific gene changes. The treatment being tested is called valemetostat tosylate, which is also known by its code name DS-3201b. This medicine works by blocking two proteins called EZH1 and EZH2, which play a role in controlling how genes are turned on and off in cancer cells. The medicine comes as a film-coated tablet that is taken by mouth.

The purpose of this study is to see how well valemetostat works in shrinking or controlling these specific types of tumors and to check how safe it is for patients. The study will measure how many patients respond to the treatment, which means their tumors get smaller or disappear. The study will also look at how long the response lasts, how long patients live without their cancer getting worse, overall survival, and any side effects that occur. Patients will be divided into different groups based on which gene change their tumor has or what type of cancer they have, such as clear cell kidney cancer, mesothelioma (a cancer that affects the lining of organs), or other types of solid tumors with these specific gene changes.

During the study, patients will take valemetostat tablets for up to 24 weeks, and possibly longer depending on how well the treatment works. Patients will have regular visits where doctors will check the size of their tumors using imaging scans and monitor their health through blood tests and physical examinations. The study will also collect tumor tissue samples to confirm the presence of the gene changes and to study how the treatment affects the cancer cells. Patients will be asked to complete questionnaires about their quality of life and any symptoms they experience. Some patients may also be asked to wear a device that tracks physical activity and other health measurements, and to participate in interviews about their experience with the treatment.

The research process

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

Step 1
Initial assessment and baseline procedures
Upon joining the study, your baseline health status will be documented. This includes a physical examination to assess your overall condition using a scoring system that measures your ability to perform daily activities.
Blood samples will be collected to check your blood cell counts, liver function, kidney function, and other important health markers. These tests must show that your body can safely tolerate the treatment.
Imaging scans, such as computed tomography (a type of detailed x-ray) or magnetic resonance imaging (a scan using magnets and radio waves), will be performed to measure your tumor. At least one tumor area must be measurable and suitable for repeated assessment throughout the study.
A pregnancy test will be performed if applicable. The test must be negative before starting treatment.
Tissue samples from your tumor will be analyzed to confirm the presence of specific genetic changes in genes such as SMARCB1, SMARCA4, ARID1A, PBRM1, BAP1, or other related genes. This confirmation is required for participation.
Step 2
Start of treatment with valemetostat
Treatment will begin on Cycle 1, Day 1. Each treatment cycle lasts a specific duration, and the cycles will continue as long as the treatment is beneficial and tolerated.
You will receive valemetostat tosylate as an oral medication in the form of film-coated tablets. The medication is taken by mouth.
The dosage, frequency, and exact duration of each cycle will be determined according to the study protocol and your individual response to treatment.
You will need to take the medication consistently as instructed throughout each treatment cycle.
Step 3
Regular monitoring during treatment
Throughout the treatment period, you will attend regular study visits for monitoring and assessment.
At these visits, blood tests will be performed to monitor your blood cell counts, liver function, kidney function, and other laboratory values. These tests check for any changes that may require dose adjustments or treatment interruption.
Your physical condition and ability to perform daily activities will be assessed at each visit.
Any side effects or health changes you experience will be recorded and evaluated according to a standardized system for classifying adverse events.
Quality of life questionnaires will be completed at designated time points to assess your well-being and any symptoms you may be experiencing.
You may be asked to complete additional questionnaires about anxiety, depression, and specific symptoms related to the treatment.
If provided, a wearable device may be used to monitor physiological parameters such as heart rate, mobility, oxygen levels, and sleep patterns.
Step 4
Tumor assessment at 24 weeks
At 24 weeks after starting treatment, imaging scans will be performed to measure changes in your tumor size and assess how the treatment is working.
The scans will be evaluated according to standardized criteria to determine if the tumor has shrunk, remained stable, or grown.
Depending on your specific type of cancer, different assessment criteria may be used to evaluate the tumor response.
The percentage change in tumor size from the beginning of the study will be calculated.
Step 5
Ongoing treatment and assessments
If the treatment is working and you are tolerating it well, you will continue taking valemetostat tosylate in repeated cycles.
Imaging scans will be performed at regular intervals throughout the treatment period to continue monitoring tumor response.
Blood tests and physical assessments will continue at scheduled visits throughout the treatment period.
Additional tissue samples or blood samples may be collected at specific time points to analyze changes in the tumor and evaluate biological markers related to treatment response.
The treatment will continue for as long as it provides benefit and remains tolerable.
Step 6
Dose modifications if needed
If you experience certain side effects, the dose of valemetostat tosylate may be temporarily stopped, reduced, or adjusted.
Any changes to your treatment dose or schedule will be determined based on the type and severity of side effects and your overall health status.
Treatment may be interrupted until side effects improve to an acceptable level, after which treatment may resume at the same or a modified dose.
Step 7
End of treatment
Treatment will end if the disease progresses, if unacceptable side effects occur, if you decide to withdraw, or if the study is completed.
Final assessments will be performed, including physical examination, blood tests, and imaging scans.
Quality of life and symptom questionnaires will be completed at the end of treatment.
Step 8
Follow-up after treatment
After stopping treatment, you will be followed for a period of time to monitor your health status and survival.
Follow-up assessments will continue to track long-term outcomes and any delayed effects of the treatment.
If applicable, contraception requirements will continue for 3 months after the last dose of study medication.
You should not donate blood for 3 months after the last dose of study medication.
If applicable, you should not donate or retrieve eggs, or freeze or donate sperm for 3 months after the last dose of study medication.

Who can join the trial?

24 criteria

You must be 18 years of age or older.
You must have a solid tumor cancer that has spread to other parts of your body (metastatic) or has come back (recurrent), confirmed by tissue examination under a microscope.
Your cancer must show specific changes in certain genes called chromatin remodeling genes (such as SMARCB1, SMARCA4, ARID1A, PBRM1, BAP1, or others), confirmed by specialized genetic testing and laboratory examination of your tumor tissue.
You must have tried and completed all other standard treatment options that are available and proven to work for your type of cancer.
Your cancer must have grown or progressed before joining this study.
You must have at least one measurable tumor that is at least 10 millimeters in size (or 15 millimeters for lymph nodes) that can be seen on imaging scans such as CT or MRI and has not been previously treated with radiation.
You must have a sample of your tumor tissue available for testing, either from a previous biopsy or surgery. If the tissue is older than 3 years or not enough is available, a new biopsy may be needed.
Your expected survival time must be at least 12 weeks.
Your ability to carry out daily activities must be good, rated as 0 or 1 on the ECOG scale (a measure of how cancer affects your daily living abilities, where 0 means fully active and 1 means some restrictions).
Your blood tests must show adequate function: white blood cells (infection-fighting cells) at least 1500 per microliter, lymphocytes (a type of white blood cell) at least 500 per microliter, platelets (blood clotting cells) at least 100,000 per microliter, and hemoglobin (oxygen-carrying protein in blood) at least 9 grams per deciliter.
Your liver function tests must be acceptable: bilirubin (a substance processed by the liver) no more than 1.5 times the normal upper limit, and liver enzymes (AST or ALT) no more than 3 times the normal upper limit, or 5 times if you have cancer spread to your liver.
Your albumin (a protein in blood) must be at least 2.5 grams per deciliter.
Your kidney function must be adequate, with creatinine clearance (a measure of how well your kidneys filter waste) at least 40 milliliters per minute.
Your blood clotting tests (INR and aPTT) must be no more than 1.5 times the normal upper limit, unless you are taking blood-thinning medications for medical reasons.
If you are a woman able to become pregnant, you must have a negative pregnancy test before starting the study.
If you are a woman able to become pregnant, you must agree to use highly effective birth control methods along with a barrier method during the study and for 3 months after the last dose of study medication.
If you are a woman able to become pregnant, you must agree not to breastfeed during the study and for 3 months after the last dose of study medication.
If you are a sexually active man with a partner who can become pregnant, you must agree to use highly effective birth control during the study and for 3 months after the last dose of study medication.
You must agree not to donate blood during the study and for 3 months after the last dose of study medication.
If you are a woman, you must agree not to donate or retrieve eggs during the study and for 3 months after the last dose of study medication.
If you are a man, you must agree not to donate or freeze sperm during the study and for 3 months after the last dose of study medication.
You must be able to understand, sign, and date the informed consent form (a document explaining the study) before any study procedures are performed.
You must be able and willing to follow the study schedule and procedures.
You must be affiliated with a social security system or have equivalent health coverage.

Who cannot join the trial?

12 criteria

You cannot participate if you have untreated brain metastases, which means cancer that has spread to your brain and has not been treated yet, or if your brain metastases are not stable
You cannot participate if you have leptomeningeal disease, which means cancer cells have spread to the thin layers of tissue covering your brain and spinal cord
You cannot participate if you are pregnant or breastfeeding
You cannot participate if you have received certain types of cancer treatments within specific time periods before joining this study
You cannot participate if you have severe heart problems or abnormal heart rhythm that could be dangerous
You cannot participate if you have serious active infections that are not controlled
You cannot participate if you have other serious medical conditions that would make it unsafe for you to join the study
You cannot participate if you have had a different type of cancer within the past 2 years, with some exceptions for certain skin cancers or other cancers that were completely removed
You cannot participate if you have severe liver or kidney problems that prevent your organs from working properly
You cannot participate if you are allergic to the study medication or its ingredients
You cannot participate if you are taking certain medications that could interfere with the study drug
You cannot participate if you have had major surgery within a certain time period before the study starts

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Verified sites

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Centre Leon Berard
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Lyon, France
Institut Curie
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Paris, France
Institut Gustave Roussy
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Villejuif, France

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Investigated drugs

Valemetostat is a medication that works by blocking certain proteins called EZH1 and EZH2 in cancer cells. These proteins can help tumors grow, so blocking them may help slow down or stop the growth of certain types of advanced solid tumors. This medicine is being tested to see if it can shrink tumors in patients with specific types of cancer.

Valemetostat Tosilate

What is already known about the treatment

Valemetostat – Valemetostat is an experimental cancer medication that works by blocking two enzymes called EZH1 and EZH2, which are involved in controlling how genes are turned on or off in cells. This drug is currently being studied in clinical trials for patients with advanced solid tumors that have specific genetic changes affecting proteins responsible for organizing DNA in cells, including certain types of ovarian and endometrial cancers. It is classified as an EZH1/2 inhibitor and belongs to a group of medications called epigenetic therapies, which target the mechanisms that control gene activity without changing the DNA sequence itself. The medication is being tested to see if it can shrink tumors or stop their growth in patients whose cancers have not responded to standard treatments.

Investigated diseases

Metastatic Solid Tumor
A metastatic solid tumor is a type of cancer that has spread from its original location to other parts of the body through the bloodstream or lymphatic system. Solid tumors are abnormal masses of tissue that form in organs or tissues, as opposed to blood cancers. When cancer cells break away from the primary tumor, they can travel to distant sites and form new tumors called metastases. The disease progresses as cancer cells continue to grow and multiply in multiple locations throughout the body. Common sites for metastases include the liver, lungs, bones, and brain. The progression varies depending on the type of original cancer and the organs affected.
Clear Cell Endometrial Carcinoma
Clear cell endometrial carcinoma is a rare and aggressive type of cancer that develops in the lining of the uterus. The cancer cells have a distinctive clear or pale appearance when viewed under a microscope due to glycogen accumulation. This type of cancer typically occurs in older women, often after menopause. The disease begins in the endometrium and can grow into the deeper layers of the uterine wall. As it progresses, the cancer may spread to nearby tissues and organs in the pelvis. Without intervention, it can metastasize to distant parts of the body through the lymphatic system or bloodstream.
Clear Cell Ovarian Carcinoma
Clear cell ovarian carcinoma is a distinct subtype of ovarian cancer characterized by cells that appear clear under microscopic examination. This cancer originates in the ovaries and is often associated with endometriosis. The tumor typically grows as a large mass within one or both ovaries. As the disease advances, cancer cells can spread to the peritoneum, which is the lining of the abdominal cavity. The cancer may also involve nearby pelvic organs and structures. In later stages, it can metastasize to distant organs such as the liver and lungs.