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). Note: treatment continued beyond disease progression because the patient derived clinical benefit, will not count as another line (limited to one oligoprogression with local ablative treatment ((stereotactic) radiotherapy / cryotherapy etc.). However, restarting a systemic therapy with an identical protocol after an interruption of >3 months will be considered as a new line of treatment.
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.
Single group
Ivonescimab
DrugIvonescimab is administered IV Q3W on Day 1 of each cycle. Ivonescimab is given at a dose of 20 mg/kg (a fixed dose of 3200 mg for ivonescimab should be used for patients ≥160 kg). The total duration of ivonescimab treatment is up to 24 months.
To assess the therapeutic value of the bispecific antibody anti-VEGF / anti-PD-1 ivonescimab as 2nd/3rd line treatment in relapsing PM patients
The analysis of the primary efficacy endpoint will be conducted in all eligible patients, based on the disease control rate (DCR) at 12 weeks according to mRECIST 1.1 for mesothelioma, which was defined as the proportion of patients with compete response (CR), partial response (PR) or stable disease (SD) at 12 weeks as assessed by the independent review committtee.
Tolerance, safety of treatment
Incidence, nature and severity of AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0).
Progression free survival (PFS)
PFS is defined as the time from date of inclusion to the earliest date of disease progression, as determined by Investigator review and review of radiographic disease assessments by IRC as per mRECIST v1.1 for mesothelioma, or death due to any cause. If a patient has not had a PFS event at the time of the analysis cut-off or at the start of any new anticancer therapy, PFS is censored at the date of last adequate tumour assessment.
Overall survival
Overall survival is defined as the time from date of inclusion to the date of death due to any cause. If a death has not been observed by the date of the analysis cut-off, OS will be censored at the date of last contact.
Best response rate
Best response rate is defined as the percentage of patients who have achieved a best response of a complete response (CR) or partial response (PR) as determined by Investigator review and review of radiographic disease assessments by IRC as per mRECIST v1.1 for mesothelioma.
Click on the lead sponsor to view all of their trials.
Intergroupe Francophone de Cancerologie Thoracique
Lead sponsor
Summit Therapeutics
Collaborator
