IVONESCIMAB for Pleural mesothelioma

Inclusion criteria

• {"criterion_text":"- 1.\tSigned Informed consent. -\tSubjects 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. -\tSubjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing."}
• {"criterion_text":"- 10.\tAdequate biological functions: Creatinine Clearance ≥45 mL/min (Cockroft or MDRD or CKD-epi); neutrophils ≥1500/mm3; platelets ≥100 000/mm3; haemoglobin ≥9 g/dL; AST and ALT <3 x ULN, total bilirubin <2 x ULN (patients with hepatic metastases or Gilbert’s syndrome must have AST and ALT ≤5 x ULN and a baseline total bilirubin ≤2 x ULN), urine protein <2+ or 24 hours urine protein quantification <1.0 g, prothrombin time (PT) or international normalized ratio (INR) ≤1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless abnormalities are unrelated to coagulopathy or are secondary to prophylactic coagulation)."}
• {"criterion_text":"- 11.\tWomen of childbearing potential and sexually active should use a highly effective contraception method within the 28 days preceding the first dose and during the 6 months following the last dose of treatment. Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug."}
• {"criterion_text":"- 12.\tFor male subjects who are sexually active with women of childbearing potential, an efficacious contraception method should be used during the treatment and during the 6 months following the last dose."}
• {"criterion_text":"- 13.\tPatient covered by a national health insurance."}
• {"criterion_text":"- 2.\tHistologically-proven Pleural Mesothelioma (no cytology allowed, biopsies by thoracoscopy recommended). Note: pathology certification by national expert network NETMESO/MESOPATH should be checked as already done in routine in France by NETMESO regional expert MTB for PM (or similar national certification if the patient had his/her PM diagnosis obtained outside France, e.g. Belgium)."}
• {"criterion_text":"- 3.\tDocumented 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)."}
• {"criterion_text":"- 4.\tMeasurable disease according to mRECIST 1.1."}
• {"criterion_text":"- 5.\tECOG PS 0 or 1."}
• {"criterion_text":"- 6.\tWeight loss <10% within 3 months of study entry."}
• {"criterion_text":"- 7.\tAge ≥18 years."}
• {"criterion_text":"- 8.\tLife expectancy >3 months."}
• {"criterion_text":"- 9.\tAvailable pathological samples (at least 10 slides from the thoracoscopy biopsies) for centralized PD-L1, MTAP, immunohistochemistry, and NGS / transcriptome analyses, all slides being centrally reviewed by the French panel MESOPATH for mesothelioma histological certification. If archival tissue is either insufficient or unavailable, the patient may still be eligible upon discussion with IFCT."}

Exclusion criteria

• {"criterion_text":"- 1.\tECOG PS>1."}
• {"criterion_text":"- 18.\tCurrent hypertension with systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after oral antihypertensive therapy."}
• {"criterion_text":"- 19.\tHistory of major diseases before registration, specifically: a)\tUnstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] classification ≥ grade 2) or vascular disease (e.g. aortic aneurysm at risk of rupture) that required hospitalization within 12 months prior to inclusion, or other cardiac impairment that may affect the safety evaluation of the study drug (e.g. poorly controlled arrhythmias, myocardial ischemia). Patients with a significant cardiac history, even if controlled, should have a LVEF >45%. b)\tHistory of oesophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses or acute gastrointestinal bleeding within 6 months before inclusion. c)\tHistory of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to inclusion. d)\tAcute exacerbation of chronic obstructive pulmonary disease within 4 weeks prior to inclusion. e)\tHistory of perforation of the gastrointestinal tract or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to inclusion."}
• {"criterion_text":"- 2.\tPrevious 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)."}
• {"criterion_text":"- 20.\tImaging during the screening period shows that the patient has: a)\tRadiologically documented evidence of major lung blood vessel invasion or encasement by cancer. b)\tRadiographic evidence of lung intratumor cavitation."}
• {"criterion_text":"- 21.\tActive uncontrolled infection including active tuberculosis, known acute viral hepatitis B and C according to serological tests. Patients with serological sequelae of cured viral hepatitis are allowed to be included. Past primary pulmonary tuberculosis in youth does not consist of a contra-indication. Past tuberculosis disease history does not represent a contraindication provided the patient was treated for at least 6 months by anti-tuberculosis antibiotic treatment."}
• {"criterion_text":"- 22.\tPatients with a known history of a positive test for HIV or known AIDS who have not received effective antiretroviral therapy (ART) for the last 4 weeks and who have an HIV viral load >200 copies/mL, regardless of CD4+ T-cell count."}
• {"criterion_text":"- 23.\tLiving attenuated vaccine received within the 30 previous days; mRNA and adenovirus vector anti-SARS-CoV2 vaccine are allowed."}
• {"criterion_text":"- 24.\tInability to comply with study or follow-up procedures as estimated by the referent investigator."}
• {"criterion_text":"- 25.\tKnown allergy or hypersensitivity to study treatment or any excipient."}
• {"criterion_text":"- 26.\tConcomitant treatment with another experimental treatment or participation in another clinical trial."}
• {"criterion_text":"- 10.\tRadiotherapy needed at initiation of treatment, except bone palliative radiotherapy on a painful or compressive tumour site (in this case, target lesions should not be selected in the irradiated zone)."}
• {"criterion_text":"- 27.\tPatient who is subject to legal protection or who is unable to express his will."}
• {"criterion_text":"- 3.\tSuspicion 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)."}
• {"criterion_text":"- 4.\tPleural effusion as the only radiological abnormality without measurable pleural thickness or mediastinal node enlargement."}
• {"criterion_text":"- 5.\tPeritoneal, pericardial or tunica vaginalis testis mesothelioma, without any pleural involvement at the time of diagnosis."}
• {"criterion_text":"- 6.\tPrevious diagnosis of adenocarcinoma from any anatomic site within the previous 3 years, with the exception of prostate adenocarcinoma history in case of localized prostate cancer with good prognostic factors according to d'Amico classification ("}
• {"criterion_text":"- 7.\tPrevious or active cancer within the previous 3 years (except for already treated in situ carcinoma of the cervix, or basal cell skin cancer, treated or not)."}
• {"criterion_text":"- 8.\tUncontrolled pleural effusion despite previous (talc or other) pleurodesis, requiring thoracocentesis (by pleural aspiration) more often than every 21 days. However, patients with efficient indwelling pleural catheter (IPC) are eligible."}
• {"criterion_text":"- 9.\tSymptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 2 weeks delay between the end of radiotherapy and the beginning of the treatment should be respected. Asymptomatic brain metastasis, not needing corticosteroids (>10 mg prednisone equivalent daily) or mannitol infusions, are allowed."}
• {"criterion_text":"- 28.\tKnown hypersensitivity to the active substance or to any of the excipients."}
• {"criterion_text":"- 11.\tHistory of previous primary immunodeficiency, organ transplantation needing an immunosuppressive treatment, any immunosuppressive drug within 28 days before registration date, or history of severe toxicity (grade 3/4) by immune mechanism linked to another immunotherapy treatment for any kind of disease."}
• {"criterion_text":"- 12.\tSystemic treatment with corticosteroids with a dose >10 mg prednisone equivalent daily, within 14 days before initiation of the treatment. Inhaled, nasal or topical corticosteroids are allowed."}
• {"criterion_text":"- 13.\tHistory of active autoimmune disease, needing systemic immunosuppressive drug, including but not limited to rheumatoid polyarthritis, myasthenia, autoimmune hepatitis, systemic Lupus, Wegener's granulomatosis, vascular thrombosis associated with anti-phospholipid syndrome, Sjogren’s syndrome with interstitial pulmonary disease, Guillain-Barré syndrome within previous 15 years, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with type I diabetes, or hypothyroidism, or immune cutaneous disease (vitiligo, psoriasis, alopecia) or benign rheumatoid polyarthritis not needing any immunosuppressive systemic treatment or >10 mg daily oral steroids, or benign sicca syndrome (Sjogren) without interstitial lung disease (ILD), or history of past Guillain-Barre syndrome beyond 15 previous years, totally reversible with no sequelae, no systemic immunosuppressive treatment during the last 20 years, are allowed to be included. Patients with Grave’s disease or psoriasis not requiring systemic therapy within the previous two years from are allowed to be included."}
• {"criterion_text":"- 14.\tActive inflammatory intestinal disease (diverticulosis, Crohn’s disease, haemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhoea."}
• {"criterion_text":"- 15.\tPre-existing moderate or severe ILD as assessed by the diagnostic CT-scan and decrease of TLCO higher than 35% from theoretical normal values linked to such ILD."}
• {"criterion_text":"- 16.\tMajor surgical procedures or serious trauma within 4 weeks prior to inclusion or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to registration."}
• {"criterion_text":"- 17.\tHistory of bleeding tendencies or coagulopathy, or clinically significant bleeding symptoms or risk within 4 weeks prior to inclusion, including but not limited to: gastrointestinal bleeding; haemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots), note: transient haemoptysis associated with diagnostic bronchoscopy is allowed; nasal bleeding / epistaxis (bloody nasal discharge is allowed); need for therapeutic anticoagulant therapy within 14 days prior to inclusion. Note: prophylactic anticoagulation for deep vein thrombosis / pulmonary embolism or to maintain venous patency is allowed."}

Primary endpoints

• {"endpoint_text":"- Disease control rate (DCR) at 12 weeks, according to RECIST 1.1 criteria modified for mesothelioma, as assessed by an Independent Review Committee (IRC) of 3 expert thoracic radiologists and oncologists","definition_or_measurement_approach":"Assessed at 12 weeks according to RECIST 1.1 modified for mesothelioma (mRECIST 1.1); assessment by an Independent Review Committee (IRC) of 3 expert thoracic radiologists and oncologists."}

Secondary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE v5.0; incidence, nature and severity recorded."}
• {"endpoint_text":"- Progression free survival (PFS) as assessed by an IRC of 3 expert thoracic radiologists and oncologists","definition_or_measurement_approach":"PFS assessed by IRC of 3 expert thoracic radiologists and oncologists."}
• {"endpoint_text":"- PFS as assessed by the local investigator","definition_or_measurement_approach":"PFS assessed by local investigator."}
• {"endpoint_text":"- PFS according to previous immunotherapy versus no previous immunotherapy","definition_or_measurement_approach":"Subgroup analysis of PFS by prior immunotherapy status (previous IO vs no previous IO)."}
• {"endpoint_text":"- PFS according to the histological subtype epithelioid vs. non-epithelioid","definition_or_measurement_approach":"Subgroup analysis of PFS by histological subtype (epithelioid vs non-epithelioid)."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured from randomization/start of treatment to death from any cause."}
• {"endpoint_text":"- Best response rate","definition_or_measurement_approach":"Best objective response rate per mRECIST/RECIST criteria as applicable."}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"Duration from first documented response to progression or death."}

France

Earliest CTIS Part Ii Submission Date

27-03-2025

Latest Decision Or Authorization Date

04-04-2025

Processing Time Days

8

Number Of Sites

20

Number Of Participants

38

Primary sponsor

Full Name

Intergroupe Francophone De Cancerologie Thoracique

Organisation Type

Patient organisation/association

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Summit Therapeutics","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"IFCT","duties_or_roles":"Monetary support","organisation_type":""}