Pembrolizumab for Malignant pleural mesothelioma | Epithelioid pleural mesothelioma | Biphasic pleural mesothelioma

Inclusion criteria

• {"criterion_text":"- Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of surgical resectable stage I-IIIA treatment-naïve epithelioid/biphasic pleural mesothelioma will be enrolled in this study.\n- Diagnosis of epithelioid/biphasic pleural mesothelioma must be histologically confirmed, preferably by video-assisted thoracoscopic surgery (VATS).\n- At screening, complete surgical resection of the mesothelioma must be deemed achievable, as assessed by a multidisciplinary evaluation.\n- The participant provides written informed consent for the trial.\n- Measurable disease, defined as at least 1 lesion measured in two positions at three separate levels on transverse cuts of CT scan that is suitable for repeated assessment using modified Response Evaluation Criteria in Solid Tumours [m-RECIST 1.1] for pleural mesothelioma is preferred; however, inclusion of specific cases without measurable disease could be discussed with the medical monitor and during the multidisciplinary team discussion of the surgical centers.\n- Histologically proved diagnosis of treatment-naive epithelioid/biphasic pleural mesothelioma.\n- Surgical resectable disease [stage I – II – IIIA (T1-3 – N0/1-M0) according to ninth TNM edition].\n- No previous surgical resection of mesothelioma.\n- Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.\n- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n- Has adequate PFT defined as an FEV1 >50% (of predicted normal volume) or ≥ 1.2 L/Sec and a DLCO >40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if pulse oximetry (O2 saturation) ≥90% room air.\n- Have adequate organ function as defined in the following table (Table 8). Specimens must be collected within 10 days prior to the start of study intervention."}

Exclusion criteria

• {"criterion_text":"- Primitive peritoneal, pericardial and tunica vaginalis testis mesotheliomas.\n- History of HIV infection. HIV testing is not required unless mandated by local health authority.\n- Cytological diagnosis of pleural mesothelioma not histologically confirmed.\n- Prior treatment with systemic anti-cancer therapy for pleural mesothelioma, prior intraoperative intracavitary chemotherapy for pleural mesothelioma, prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.\n- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.\n- Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.\n- Has uncontrolled, potentially reversible cardiac conditions, as Investigator’s judgment (eg. Unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation > 500 millisecond) or participants with congenital long QT syndrome.\n- Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.\n- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.\n- Known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or adequately treated carcinoma in-situ without evidence of disease are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.\n- Subject incapacitated to understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted\n- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.\n- Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid).\n- History of Hepatitis B (defined as HbsAg reactive) or known active Hepatitis C virus (defined as detectable HCV RNA [qualitative]) infection. Note: Testing for Hepatitis B or C is not required unless mandated by local health authority.\n- Has not adequately recovered from major surgery or has ongoing surgical complications.\n- Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.\n- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.\n- Has had an allogenic tissue/solid organ transplant."}

Primary endpoints

• {"endpoint_text":"- Pathological complete response defined as 0% residual viable tumor cells in the primary tumor and in sampled lymph nodes, following neoadjuvant treatment as assessed by central pathology assessment. Patients who are not evaluable per central pathology assessment or who do not have a surgical specimen will be considered as non-pCR. Patients who received less than 2 cycles out of the planned 3 cycles of neoadjuvant therapy due to unacceptable toxicity will not be considered in the pCR evaluation.","definition_or_measurement_approach":"Assessed by central pathology assessment; defined as 0% residual viable tumor cells in the primary tumor and in sampled lymph nodes. Patients not evaluable per central pathology assessment or without a surgical specimen considered non-pCR. Patients who received less than 2 of the planned 3 cycles due to unacceptable toxicity will not be considered in the pCR evaluation."}

Secondary endpoints

• {"endpoint_text":"- Major pathological response defined as ≤10% residual viable tumor cells in the primary tumor and sampled lymph nodes after neoadjuvant treatment at the time of resection as assessed per central pathology laboratory. Patients who are not evaluable per central pathology assessment (including patients with R2 margins) or who do not have a surgical specimen will be considered as having non-mPR (eg, response captured as “non-evaluable” or “missing,” as appropriate).","definition_or_measurement_approach":"Assessed per central pathology laboratory; ≤10% residual viable tumor cells in primary tumor and sampled lymph nodes; non-evaluable or missing cases considered non-mPR."}
• {"endpoint_text":"- Overall response rate defined as the sum of partial and complete response according to modified RECIST 1.1 criteria for Malignant Pleural Mesothelioma.","definition_or_measurement_approach":"Measured using modified RECIST 1.1 criteria for Malignant Pleural Mesothelioma; ORR = sum of partial and complete responses."}
• {"endpoint_text":"- Event free survival defined as the time from the start of treatment to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause.","definition_or_measurement_approach":"Time-to-event measure from treatment start to progression events precluding surgery, progression/recurrence after surgery, progression without surgery, or death."}
• {"endpoint_text":"- Overall survival defined as the time from the start of treatment to all-cause death.","definition_or_measurement_approach":"Time from treatment start to death from any cause."}
• {"endpoint_text":"- Feasibility in terms of: i) Resection rate: defined as the percentage of patients finally eligible for radical surgery, among those who receive at least one cycle of neoadjuvant treatment; ii) rate of patients who complete three cycles of neoadjuvant chemo-immunotherapy followed by radical surgery.","definition_or_measurement_approach":"Resection rate = percentage eligible for radical surgery among those receiving ≥1 cycle of neoadjuvant treatment; completion rate = percentage completing three cycles of neoadjuvant chemo-immunotherapy followed by radical surgery."}
• {"endpoint_text":"- Safety profile in terms of incidence and grade of adverse events; incidence of adverse events and serious adverse events; incidence of definitive interruptions of treatment because of any-cause adverse events and treatment-related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.","definition_or_measurement_approach":"Safety assessed by incidence and grade of AEs and SAEs and treatment interruptions, using CTCAE v5.0."}

Italy

Earliest CTIS Part Ii Submission Date

03-07-2024

Latest Decision Or Authorization Date

29-08-2024

Processing Time Days

57

Number Of Sites

9

Number Of Participants

40

Primary sponsor

Full Name

Istituto Oncologico Veneto

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Depo - Pack Srl","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"MSD International GMbH","duties_or_roles":"Source of monetary support","organisation_type":""}