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Each CST will use a Bayesian Optimal Phase II (BOP2) design which incorporates at least one ‘go/no-go’ interim analysis, this minimises the projected sample size if a low number of patients displaying disease control rate (DCR) is observed. Once each trial arm reaches the required sample size, we can conclude whether the treatment is acceptable, in terms of activity at a pre-determined DCR rate, safety and feasibility of use, and so warrants further evaluation in a future randomised trial.

Based on a one-sided type I error rate of no more than 0.05, a sample size of 26 provides power of approximately 0.83 under the Bayesian Optimal Phase 2 (BOP2) design. This considers an interim analysis for futility (not pausing recruitment) after 13 patients, and a null hypothesis that the 12-week DCR is 0.25 (i.e., a true DCR of 25% at 12 weeks would be too low, requiring no further evaluation) against an alternative hypothesis that the DCR is 0.5 (i.e., a true DCR of 50% at 12 weeks would be sufficient to warrant further evaluation).

The BOP2 design recommends stopping for futility if 3 or fewer patients out of 13 achieve disease control. The numbers for the interim analysis are to provide guidance to the Trial Management Group and may be overruled if there are other possible reasons (e.g., toxicity) that outweigh the recommendation to stop or continue.

The primary endpoint is the proportion of patients who have achieved disease control (complete response, partial response, or stable disease) assessed by mRECIST 1.1 at 12 weeks. A total of 11 patients achieving disease control or more in the 26 patients will suggest that the treatment is sufficiently effective.

Trial Status:

Open to recruitment (SELECTmeso1)

Population:

Patients with confirmed histological diagnosis of mesothelioma (any histology) with evidence of MTAP loss on immunohistochemistry, and evidence of disease progression following prior standard systemic therapy on CT scan.

Inclusion:

• Histological confirmation of malignant mesothelioma (pleural, or non-pleural)
• Evidence of disease progression on CT scan
• Available archival tissue block for molecular screening
• Previous treatment with at least 1st line licenced systemic anti-cancer therapy. Patients can have received more than one prior line of systemic therapy
• ECOG performance status 0-1
• Expected survival of ≥12 weeks

Exclusion:

• No progressing CNS disease and not receiving any concurrent systemic therapy at the time of screening
• 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)
• New York Heart Association Class II or greater congestive heart failure
• Patients requiring long term oxygen therapy
• 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 participant’s ability to participate in the trial
• Patients on active treatment in another clinical trial

Additional eligibility will be defined for each CST.

Funder

Each CST will be funded separately, currently CST1 is funded by Asthma and Lung UK.