Multicentre, open-label, single arm phase II study for patients with PM previously treated by immunotherapy and standard chemotherapy. 38 patients will be given second or third-line treatment with ivonescimab 20mg/kg every 3 weeks.
An estimated 38 patients will be enrolled in approximately 20 centres. Patients will be treated for a maximum of 2 years, until disease progression, unacceptable toxicity, withdrawal of consent or another discontinuation criterion is met.
The null hypothesis is disease control rate (DCR) at 12 weeks ≤ 30%. The alternative hypothesis is DCR ≥ 55% at 12 weeks.
Signed Informed consent. Subjects must have signed and dated an IEC 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 subject care.
Histologically-proven Pleural Mesothelioma (no cytology allowed, biopsies by thoracoscopy recommended).
Documented progression by CT with iodine injection according to modified RECIST 1.1 for mesothelioma (mRECIST 1.1; pleural thickness perpendicular to the chest wall or mediastinum of 7mm or more, on 2 positions, at 3 separate levels on transverse cuts of CT-scan, at least 1cm apart, the sum of 6 measurements defining a pleural unidimensional measure), or according to RECIST 1.1 for mediastinal nodes or metastatic lesion, after maximum 2 lines including immunotherapy by nivolumab ± ipilimumab, and standard P/P chemotherapy [with (maximum 40% total of patients) or without bevacizumab], sequentially (regardless of treatment order), or first-line combining standard chemotherapy + IO (pembrolizumab or other IO investigational drug but no anti-angiogenic drug).
Measurable disease according to mRECIST 1.1.
ECOG PS>1.
Previous treatment for PM by more than 2 lines of systemic treatment, or by bevacizumab (or another anti-angiogenic / anti-VEGF pathway drug) except if combined with P/P chemotherapy [scheme validated by ASCO, NCCN, and ESMO guidelines] in maximum 40% of the total of recruited patients (n=15).
Suspicion of hyperprogressive disease or rapid tumour progression when treated by previous IO (i.e. progressive disease within 9 weeks of treatment by previous nivolumab ± ipilimumab or alternative immunotherapy, starting from C1D1 or from randomization if previous experimental immunotherapy).
Pleural effusion as the only radiological abnormality without measurable pleural thickness or mediastinal node enlargement.
Intergroupe Francophone de Cancerologie Thoracique
Lead sponsor
Summit Therapeutics
Collaborator