Actively Recruiting
Efficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.
Led by Gustave Roussy, Cancer Campus, Grand Paris · Updated on 2026-04-21
900
Participants Needed
4
Research Sites
312 weeks
Total Duration
On this page
Sponsors
G
Gustave Roussy, Cancer Campus, Grand Paris
Lead Sponsor
D
Daiichi Sankyo Co., Ltd.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Rational, objective and design: Some cancer-protecting genes are inactivated when the EZH2 enzyme is too active or the SWI/SNF complex is less active. The EZH1/2 enzymes and the SWI/SNFs complex play opposing roles in gene expression: we hypothesize that valemetostat, an inhibitor of the EZH1/2 enzymes, will stop/slow down the growth of cancer cells by reactivating these genes. Numerous clinical trials are currently underway worldwide to optimize the development of valemetostat tosylate and potentially offer a new targeted therapeutic option for patients suffering from various cancer pathologies. The aim of this research is to evaluate the efficacy of valemetostat on solid tumors, which have an alteration in certain genes: SMARC (B1/A4/A2/C1/C2), ARID (1A/1B), PBRM1, BAP1 and other SWI/SNF sub-units. The research will be conducted in two phases: 1) Pre-selection of patients with the desired alterations. 2) Treatment with valemetostat, 200mg/day, for a maximum of 2 years, with examinations every 28 days. This is a multicenter, international, phase II open-label, multicenter modular study exploring the efficacy and safety of valemetostat. Module 1 will be the SWI/SNF basket monotherapy study describe below. Such design will allow the study to evolve considering signals for further monotherapy and/or combination modules. The Primary endpoint of the study is Overall Response Rate at 24 weeks, defined as the proportion of patients with a confirmed best overall response. Trial population: Adult patients with histologically/cytologically confirmed progressive metastatic or recurrent solid tumor, who have selected chromatin remodeling deficiency in at least one of the following genes: SMARCB1, SMARCA4, SMARCA2, SMARCC1, SMARCC2, ARID1A, ARID1B, PBRM1, BAP1and other SWI/SNF sub-units; or molecularly (Wildtype) and phenotypically-selected Clear cell endometrial or ovarian carcinoma cancers. Patients must be using an effective method of contraception and have signed the consent form. They must not participate in another clinical study with an investigational product during the last 3 weeks, during the study treatment and not have a contraindication to the study treatment (…) Intervention: After confirmation by IHC of the loss of expression in tumors cells of SMARCB1, SMARCA4, SMARCA2, SMARCC1, SMARCC2, ARID1A, ARID1B, PBRM1, BAP1and other SWI/SNF sub-units and validation of inclusion/exclusion criteria patients will included in different cohorts (refer to investigation scheme). All patients will receive Valemetostat (200 mg per day), divided into 28-day periods called treatment cycles, for a maximum of two years. The main interventions scheduled are blood samples (to evaluate biological parameters and for translational research), electrocardiogram, echocardiography and CTscan. For patients who have consented, sequential biopsies will be performed as follow: at baseline, on treatment and at progression. Ethical consideration: This research will make it possible to collectively evaluate the interest of EZH1/2 inhibitor in solids tumors with SWI/SNF defect. Individually, by participating in this research, patients could benefit from these treatments based on cell-based results and in the treatment of relapsed/refractory peripheral T-cell lymphomas, with an improvement in symptoms and quality of life. As with any research, the investigational drug and other procedures that take place may involve risks, some of which are already known and others not yet described. The main risks (described in the consent form) are side effects of the valemetostat. If they agree, patients will also be monitored more closely with their safety assessed through patient-reported outcomes (PRO), the evaluation of their experience through qualitative interviews \& assessment of quality of care and the evaluation of their biometric physiological via a wearable device.
CONDITIONS
Official Title
Efficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patient understands and signs the informed consent form before any study procedures.
- Ability to follow the study protocol.
- Age 18 years or older.
- Histologically or cytologically confirmed progressive metastatic or recurrent solid tumor.
- Disease progression before entering the trial.
- Exhausted all other effective standard treatments.
- Availability of sufficient tumor tissue for testing or willingness to have a new biopsy.
- Documented bi-allelic deletion of specific SWI/SNF genes or molecularly selected clear cell endometrial or ovarian carcinoma.
- At least one measurable lesion suitable for repeated assessment.
- ECOG performance status of 0 or 1 with no worsening at enrollment.
- Estimated life expectancy over 12 weeks.
- Adequate blood counts and organ function based on recent lab tests.
- Negative pregnancy test for women of childbearing potential and agreement to use effective contraception during and after the study.
- Agreement not to breastfeed during and for 3 months after the study.
- Agreement to use contraception for sexually active males with partners of childbearing potential.
- Agreement not to donate blood or sperm during and for 3 months after the study.
- Ability and willingness to attend study visits and procedures.
- Affiliation with a social security or equivalent system.
You will not qualify if you...
- Participation in another clinical trial with an investigational drug within the last 4 weeks.
- Receiving anti-cancer therapy within 21 days before starting study drug.
- Recent radiation therapy affecting over 20% of bone marrow or major surgery within 4 weeks.
- History of another primary cancer within 5 years, with some exceptions.
- Recent use of systemic immunosuppressive drugs within 2 weeks before study start.
- Ongoing severe side effects from previous treatments (except hair loss).
- Severe allergic reactions to similar drugs or valemetostat components.
- Uncontrolled or significant cardiovascular disease.
- Positive HIV test or active hepatitis B or C infection.
- Active tuberculosis or uncontrolled infections requiring IV treatment.
- Other uncontrolled systemic diseases.
- Use of moderate or strong CYP3A inducers.
- Live vaccine administration within 4 weeks prior to study start, except COVID-19 vaccines.
- Major surgery within 20 days prior to study start or planned during study.
- Uncontrolled tumor-related pain or effusions requiring frequent drainage.
- Uncontrolled high calcium levels.
- History of leptomeningeal disease or symptomatic/unstable brain metastases.
- Spinal cord compression not stable for at least 2 weeks prior to study.
- Pregnancy, breastfeeding, or unwillingness to use birth control.
- Prior treatment with EZH1/2 inhibitors except in certain cohorts.
- Any condition interfering with study treatment or safety evaluation.
- Legal incapacity or inability to give consent.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 4 locations
1
Gustave Roussy
Villejuif, Val de Marne, France, 94805
Actively Recruiting
2
Institut Bergonié
Bordeaux, France, 33076
Not Yet Recruiting
3
Centre Léon Berard
Lyon, France, 69373
Not Yet Recruiting
4
Institut Curie
Paris, France, 75005
Not Yet Recruiting
Research Team
S
Sophie Postel-Vinay, MD, PhD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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