Clinical trial NCT05005429: Study of the Efficacy and Safety of the Bintrafusp Alfa in Previously Treated Advanced Malignant Pleural Mesothelioma
Official title: A Phase II Single Arm Clinical Trial Assessing the Efficacy and Safety of BIntrafusp Alfa (M7824) in Previously Treated Advanced Malignant Pleural MESothelioma (BIMES)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mesothelioma; Lung
Keywords: Malignant pleural mesothelioma
Bintrafusp alfa
Lead sponsor: Fundación GECP
Sponsor class: OTHER
First posted: 2021-08-13
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, non-randomized, phase II, single arm, multi-center controlled clinical trial.

47 patients will be enrolled in this trial to determine the efficacy and safety of Bintrafusp alfa (M7824) in advanced malignant pleural mesothelioma patients previously treated with platinum-based chemotherapy.

Detailed description: This is an open-label, non-randomized, phase II, single arm, multi-center controlled clinical trial.

Patients enrolled will receive Bintrafusp alfa (M7824) 1200mg intravenous. The treatment will be administered at day 1 of 14-day intervals.Treatment will be administered until unacceptable toxicity, loss of clinical benefit, disease progression or completion of 2 years of therapy.

The primary objective is to determine the efficacy of M7824 in terms of the Progression Free Survival (PFS) assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1.

Patient accrual is expected to be completed within 1.5 years excluding a run-in-period of 3-6 months. Treatment and follow-up are expected to extend the study duration to a total of 3.5 years. Patients will be followed 1 month after treatment. The study will end once survival follow-up has concluded.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects aged ≥ 18 years and capable of giving signed informed consent or requirement per local legislation.
* ECOG performance status of 0-2.
* Histologically confirmed malignant pleural mesothelioma (all histological subtypes are eligible), unresectable advanced or metastatic.
* Patients that progressed or be intolerant to ≤ 2 regimens of chemotherapy, including platinum-based chemotherapy with pemetrexed. Prior bevacizumab treatment given during chemotherapy are allowed.
* Evaluable disease or measurable disease as assessed according to the modified RECIST v1.1 criteria.
* Availability of tumor tissue for translational research (at least 10 slides); Archival tumor tissue at diagnosis can be sent if it was obtained less than 18 months ago.
* Life expectancy of at least 3 months.
* Adequate hematologic and organ function defined by the following laboratory results obtained within 14 days prior to enrollment:

Hematologic: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL Hepatic: Total bilirubin level ≤ the upper limit of normal (UNL) range, AST and ALT levels ≤ 1.5 x ULN and ALP ≤ 2.5 x ULN. For participants with liver involvement in their tumor, AST ≤5 x ULN, ALT ≤ 5 x ULN, and bilirubin ≤ 3.0 x ULN.

Renal: Creatinine level ≤1.5 x ULN or estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) For participants with Creatinine \> 1.5 x ULN, glomerular filtration rate (GFR) can also be used.

Coagulation: normal international normalized ratio (INR), PT ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.

* Stable HIV infection on ART for at least 4 weeks, no documented evidence of multi-drug resistance, viral load of \< 400 copies/ml and CD4+ T-cells ≥ 350 cells/μL.
* Controlled HBV/HCV infection on a stable dose of antiviral therapy, HBV viral load below the limit of quantification. HCV viral load below the limit of quantification.
* All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention.
* For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate (\< 1% per year) when used consistently and correctly throughout the study and for at least 2 months after last bintrafusp alfa treatment administration .
* For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate \[\< 1% per year\] when used consistently and correctly.
* Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 8 days prior to initiation of study drug.

Exclusion Criteria:

* Prior immune checkpoint therapy with an anti-PD-1, anti-PD-L1, anti-CD137, or anti-CTLA-4 antibody.
* Known severe hypersensitivity \[Grade ≥ 3 NCI CTCAE 5.0\]) to investigational product or any component in its formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma.
* Previous malignant disease (other than the target malignancy to be investigated in this study) within the last 3 years. Participants with a history of cervical carcinoma in situ, superficial or noninvasive bladder cancer, localized prostate cancer or basal cell or squamous cell carcinoma in situ previously treated with curative intent and endoscopically resected GI cancers limited to the mucosal layer without recurrence in \> 1 year are NOT excluded.
* Active central nervous system (CNS) metastases and/or carcinomatous meningitis that require therapeutic intervention or are causing clinical symptoms. Patients with previously treated brain metastases may participate provided the participants are stable and are not using steroids for at least 7 days prior to randomization.
* Prior major surgery within 4 weeks prior to the first dose of study intervention.
* Unstable or unresolved surgical or chemotherapy-related toxicity that would compromise the patient's capacity to participate in the trial. Persisting Grade \> 1 NCI CTCAE 5.0 toxicity (except alopecia and vitiligo) related to prior therapy; however, sensory neuropathy Grade ≤ 2 is acceptable.
* Prior organ transplantation including allogenic stem-cell transplantation, except transplants that do not require immunosuppression.
* Live vaccines given 30 days prior to first dose of protocol treatment (M7824). Seasonal flu vaccines that do not contain a live virus are permitted. Also, COVID-19 vaccines approved by the authorities that do not contain live virus are permitted.
* Drug-induced interstitial lung disease (ILD) or participant has had a history of drug-induced pneumonitis that has required oral or IV steroids, and/or other diseases, which in the opinion of the Investigator might impair the participant's tolerance for the study or ability to consistently participate in study procedures.
* Active and serious autoimmune disease that might deteriorate upon treatment with immunotherapy. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) or topical therapy (e.g., steroids) for psoriasis or eczema is not considered a form of systemic treatment.
* Ongoing clinically serious infections requiring systemic antibiotic or antiviral, antimicrobial, or antifungal therapy.
* Known history of active tuberculosis or any active infection requiring systemic therapy.
* Patients with diagnosed immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
* Clinically significant cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
* History of bleeding diathesis or recent major bleeding events (i.e. Grade ≥ 2 bleeding events in the month prior treatment)
* Patients with any serious underlying medical condition that might impair patient's capacity to participate in the trial.
* Substance or alcohol abuse, medical, psychological or social conditions that may interfere with the patient's participation in the trial or evaluation of the trial results.
* Women who are pregnant or in the period of lactation.

Primary outcomes:
measure: To evaluate the efficacy of the treatment
timeFrame: From the date of randomization to the date of last follow up, assessed up to 24 months
Secondary outcomes:
measure: To evaluate the Overall Response Rate (ORR) of the treatment
timeFrame: From the date of randomization to the date of last follow up, assessed up to 24 months
measure: To evaluate the Overall survival (OS) rate
timeFrame: From the date of randomization to the date of last follow up, assessed up to 24 months
measure: To determinate duration of response
timeFrame: From the date of confirmed response to last follow up, assessed up to 24 months
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: From the subject's written consent to participate in the study through 30 days after the final administration of the drug
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: ICO Badalona, Hospital Germans Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: ICO Hospitalet
state: Barcelona
city: A Coruña
country: Spain
facility: Hospitalario Universitario A Coruña
state: La Coruña
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d' Hebron
city: Barcelona
country: Spain
facility: Hospital Parc Taulí
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Girona
country: Spain
facility: ICO Girona, Hospital Josep Trueta
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Málaga
country: Spain
facility: Hospital Universitario Virgen De La Victoria
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
Study officials:
affiliation: Fundación GECP President
name: Mariano Provencio, MD
role: PRINCIPAL_INVESTIGATOR
References: