Relapsed malignant mesothelioma Cancer
Conditions
Interventions
Current interventions as of 29/05/2025:
Mesothelioma patients with evidence of MTAP deficient relapsed mesothelioma on immunohistochemistry, and evidence of disease progression following prior stand
Sponsors
University of Southampton
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 29/05/2025: Platform: 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 4. Previous treatment with at least 1st line licenced systemic anti-cancer therapy. Patients can have received more than one prior line of systemic therapy 5. No progressing CNS 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 FFPE 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 11. Optional: Consent to store tissue for future research SELECTmeso1: 1. Evidence of MTAP deficient relapsed mesothelioma 2. Willing to consent and able to undergo required procedures to provide blood 3. Adequate organ function, including the following: 3.1.. Adequate bone marrow reserve: 3.1.1. Absolute neutrophil count (ANC) = 1.5 x 109/L 3.1.2. WBC =3 x 109/L 3.1.3. Haemoglobin =85 g/L 3.1.4. Platelet count =100 × 10e9/L 2. Adequate liver function and renal: 2.1. Bilirubin 45 ml/min 3. INR =1.5 × institutional ULN unless on a stable dose of an anticoagulant with no unexplained elevation of INR 4. 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. 5. 18 years of age and older _____ Previous inclusion criteria: Platform: 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 4. Previous treatment with at least 1st line licenced systemic anti-cancer therapy. Patients can have received more than one prior line of systemic therapy 5. ECOG performance status 0-1 6. 16 years of age and older 7. Expected survival of =12 weeks 8. Consent to provide baseline FFPE tumour tissue sample for trial 9. 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 10. Optional: Consent to store tissue for future research SELECTmeso1: 1. Evidence of MTAP loss with wildtype p53 2. Willing to consent and able to undergo required procedures to provide blood 3. Adequate organ function, including the following: 3.1.. Adequate bone marrow reserve: 3.1.1. Absolute neutrophil count (ANC) = 1.5 x 109/L 3.1.2. WBC =3 x 109/L 3.1.3. Haemoglobin =85 g/L 3.1.4. Platelet count =100 × 10e9/L 2. Adequate liver function and renal: 2.1. Bilirubin 45 ml/min 3. INR =1.5 × institutional ULN unless on a stable dose of an anticoagulant with no unexplained elevation of INR 4. 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 be
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 29/05/2025: Platform: 1. No progressing CNS disease and not receiving any concurrent systemic therapy at the time of screening 2. 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) 3. New York Heart Association Class II or greater congestive heart failure 4. Patients requiring long term oxygen therapy 5. Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participants’s ability to participate in the trial 6. Patients on active treatment in another clinical trial SELECTmeso1: 1. MTAP-negative tumours not confirmed via IHC testing performed by the central lab. 2. Diagnosis, detection, or treatment of another type of cancer 5 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin, superficial non-muscle invasive bladder cancer that has been definitively treated), or prostate or cervical cancer in remission. 3. Have received treatment with an agent that has no marketing authorisation, within 14 days of study entry. If the patient has participated in a different SELECTmeso CST, they must comply with the washout period for that CST. 4. Patients of child-bearing potential who are not able to use at least one method of highly effective contraception (as detailed in section 5.3) 5. Patients who are pregnant or breast feeding 6. Uncontrolled CNS disease. Asymptomatic brain metastases are allowed if previously treated with radiotherapy >28 days prior to starting brigimadlin (BI 907828). 7. Palliative radiotherapy within the mRECIST 1.1 area in the 4 weeks prior to baseline CT scan. 8. Patients with severe hepatic insufficiency or severe renal impairment. 9. The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. 10. Patient has any of the following cardiac criteria: 10.1. Mean resting corrected QT interval (QTcF) >470 msec 10.2. Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block 10.3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval. 10.4. Ejection fraction (EF) <50% or the lower limit of normal of the institutional standard. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF, will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram, multi-gated acquisition scan). A historic measurement of EF no older than 6 months prior to first administration of trial drug can be accepted provided that there is clinical evidence that the patient’s cardiac disease has not significantly worsened since this measurement in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease control rate assessed using mRECIST 1.1 for mesothelioma at 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Disease control rate assessed using mRECIST 1.1 for mesothelioma at 24 weeks 2. Time-to-event data for overall survival (OS) and progression-free survival (PFS) up to 24 weeks will be presented using Kaplan-Meier curves. Median OS and PFS (with 95% confidence intervals) will be reported along with 12- and 24-week overall and progression-free survival. OS will also be collected up to 24 weeks plus 30 days. 3. Safety and tolerability reported in accordance with the NCI common terminology criteria for adverse events version 5. Adverse events will be collected up to 24 weeks plus 30 days. | — |
Countries
United Kingdom
Outcome results
None listed