Mesothelioma
Conditions
Keywords
MTAP, SELECTmeso, Meso
Brief summary
By incorporating a platform trial protocol design, SELECTmeso will spearhead a next-generation precision medicine trial platform in relapsed mesothelioma for the UK enabling early evaluation of hypothesis-driven targeted therapies. The SELECTmeso Platform trial protocol allows incorporation of a range of identified and yet-to-be-identified candidates as potential treatments for patients with relapsed mesothelioma into the platform. Candidate Specific Trials (CSTs) will be added into the trial via treatment-specific CSTs of this platform trial protocol as appendices. Having one platform trial protocol ensures different candidates are evaluated in the same consistent manner and that opening up new trials for new candidates is more efficient. SELECTmeso1 is our first Candidate Specific Trial (CST) on the platform. SELECTmeso1 is investigating if a drug called BMS-986504 is effective in shrinking mesothelioma tumours as a targeted treatment for patients with tumours that have specific genetic biomarkers. Biomarkers are molecules that can indicate normal or abnormal processes taking place in the body or tumour, they can indicate how effective certain treatments will be. BMS-986504 has shown to be tolerated and promising signs of activity on patients with MTAP-deficient solid tumours, in a previous mesothelioma trial.
Detailed description
SELECTmeso Platform: Participants will consent to the platform and some of the tissue collected from a previous biopsy will be analysed in a laboratory to find out which biomarkers are present in the tumour. Participants will not need to provide any more tissue or attend hospital for this step. Depending on the biomarker(s) present, the participant will then be offered the opportunity to take part in a study looking at a drug that is thought to be best for that biomarker, or possibly a drug for patients without any biomarkers. If following this screening step, the participant is not eligible for any treatments, they will return to standard care with their doctor. They may be contacted regarding future treatments within the SELECTmeso trial if new treatments are added that they would be eligible for. SELECTmeso1: This is the first Candidate Specific Trial on the SELECTmeso platform and is investigating if a drug called BMS-986504 is effective in shrinking mesothelioma tumours in participants with MTAP-deficient solid tumours. Once participants are screened and confirmed eligible, they will start treatment with BMS-986504 which will be administered orally in the form of a 3 tablets once a day. Participants will take a 600mg dose. Participants will have a clinic visit every 21 days where they will have routine blood tests and assessment to monitor their health. Some clinic visits will include additional trial bloods. During treatment, participants will have CT scans (computerised tomography scan) every 6 weeks to monitor the effect of the treatment. These are the same type of scans and frequency they would have normally to monitor their health. Treatment will stop after a maximum of 24 weeks (8 cycles) and participants will have an end of treatment visit, followed by a safety visit 30 days later.
Interventions
DRUGBMS-986504
BMS-986504 - next-generation MTA-cooperative PRMT5 inhibitor
Sponsors
University of Southampton
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
SELECTmeso Platform Inclusion Criteria: 1. Histological confirmation of malignant mesothelioma (pleural, or non-pleural) 2. Evidence of disease progression on CT scan 3. Available archival tissue block for molecular screening or existing molecular screening result via validated NHS diagnostic grade immunohistochemistry-based assays 4. Previous treatment with at least 1st line licensed systemic anti-cancer therapy. Patients can have received more than one prior line of systemic therapy 5. No progressing central nervous system disease and not receiving any concurrent systemic therapy at the time of screening 6. ECOG performance status 0-1\* 7. 16 years of age and older 8. Expected survival of ≥12 weeks 9. Consent to provide baseline tumour tissue sample for trial 10. Patients must have signed and dated a REC-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal patient care SELECTmeso1 Inclusion Criteria: A. Evidence of MTAP deficient. MTAP deficiency detected by a validated immunohistochemistry test conducted under the SELECTmeso master protocol, in the Leicester NHS pathology department B. Willing to consent and able to undergo required procedures to provide blood C. 18 years of age and older D. Adequate organ function, including the following: 1. Adequate bone marrow reserve: i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, ii. WBC ≥ 3 x 109/L, iii. Haemoglobin ≥ 85g/L, iv. Platelet count ≥100 × 109/L 2. Adequate liver function and renal: i. Bilirubin \< 1.5 x ULN ii. AST \& ALT \<3 x ULN iii. Creatinine clearance \> 45ml/min. 3. INR ≤ 1.5 × institutional ULN unless on a stable dose of an anticoagulant with no unexplained elevation of INR E. Participants must provide informed consent to SELECTmeso1 before any study specific procedures. The PI must confirm the eligibility of a participant in the participant's medical notes before enrolment F. Women of childbearing potential (WOCBP) participants agree to use contraception (see Section 5.3) while participating in this study, and for a period of 6 months after the last dose of study treatment G. Men whose partner is a WOCBP agree to use contraception (see Section 5.3) while participating in this study, and for a period of 6 months after the last dose of study treatment SELECTmeso Platform
Exclusion criteria
1. Patients with a diagnosis of a second malignancy (except prostate or cervical cancer in remission, patients with a diagnosis of basal cell carcinoma or non-muscle invasive bladder cancer, who can all be included) 2. New York Heart Association Class II or greater congestive heart failure 3. Patients requiring long term oxygen therapy 4. Any other significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial 5. Patients on active treatment in another clinical trial SELECTmeso1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| SELECTmeso Platform : Molecular profiling of participant's tumour block SELECTmeso1: Disease Control Rate (DCR) using RECIST 1.1 at 12 weeks. | SELECTmeso Platform: Baseline SELECTmeso1: at 12 weeks of treatment |
Secondary
| Measure | Time frame |
|---|---|
| SELECTmeso Platform: Further translational research on participant's tumour block SELECTmeso1: Disease control rate using RECIST 1.1 at 24 weeks. | SELECTmeso Platform: through study completion, an average of 1 year SELECTmeso1: 24 weeks of treatment |
Countries
United Kingdom
Outcome results
None listed