This is a multicentre, phase IIR, double non-comparative arm trial, with an initial safety run for the anti-LAG3 arm.
Approximately 40 sites will participate in the study and will enroll 126 patients with treatment-naive, unresectable malignant PM.
Treatment will be administered in 21-day cycles and will continue until disease progression, unacceptable toxicity, withdrawal of consent or for 2 years immunotherapy maximum.
Once the patient discontinues study treatment, the treatment period will end and the patient will enter the follow-up period. No cross-over is allowed between arms.
Signed written 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.
Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
Histological diagnosis (no cytology allowed, thoracoscopy biopsy recommended).
ECOG PS>2.
Previous cancer treatment including chemotherapy or immunotherapy with anti-PD-1, anti-PD-L1, Anti-CTLA4 or any ICI antibody.
Pleural effusion as the only radiological abnormality without measurable pleural thickness or mediastinal node enlargement.
Peritoneal, pericardial or tunica vaginalis testis mesothelioma.
Parallel
Cemiplimab
Drug350mg every 3 weeks for up to 24 months.
Fianlimab
Drug1600mg every 3 weeks for up to 24 months.
Pemetrexed (Alimta)
Drug500 mg/m² every 3 weeks for 6 cycles.
Cisplatin
Drug75 mg/m² every 3 weeks for 6 cycles.
Carboplatin (AUC 5)
DrugAUC 5 (recommended maximum dose of 800 mg) every 3 weeks for 6 cycles.
To evaluate the activity of the combination of double immunotherapy anti-LAG3+ anti-PD-1 and pemetrexed+platinum chemotherapy
The primary endpoint is 6-month disease control rate (DCR). The analysis will be conducted in the FAS population. DCR is defined as the proportion of patients who have achieved at 6 months an overall response of CR, PR or stable disease (SD), as assessed by an independant review committee (IRC) per RECIST v1.1 modified for mesothelioma.
Tolerance, safety of treatment
Incidence, nature, and severity of adverse events (AE), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). The rate of Hyper-Progressive Disease (HPD) will also be calculated.
Progression Free Survival (PFS) as assessed by an IRC
PFS is defined as the time between the date of randomisation and the first date of documented progression, as assessed by investigator and an IRC per RECIST v1.1 modified for mesothelioma, or death due to any cause, whichever occurs first.
PFS as assessed by the investigator
PFS is defined as the time between the date of randomisation and the first date of documented progression, as assessed by investigator and an IRC per RECIST v1.1 modified for mesothelioma, or death due to any cause, whichever occurs first.
PFS according to the histological subtype epithelioid vs. non-epithelioid
PFS is defined as the time between the date of randomisation and the first date of documented progression, as assessed by investigator and an IRC per RECIST v1.1 modified for mesothelioma, or death due to any cause, whichever occurs first. PFS will be analysed according to the histological subtype.
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Intergroupe Francophone de Cancerologie Thoracique
Lead sponsor
Regeneron Pharmaceuticals
Collaborator
