Study of the Efficacy and Safety of the Bintrafusp Alfa in Previously Treated Advanced Malignant Pleural Mesothelioma

NCT ID: NCT05005429

Last Updated: 2025-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-20
• Study Completion Date: 2024-02-01

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.

Conditions

Mesothelioma; Lung

Keywords

Malignant pleural mesothelioma; Bintrafusp alfa

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: Bintrafusp alfa (M7824)

Bintrafusp alfa (M7824): 1200mg, over 60 minutes IV infusion The treatment will start within 1-5 days from enrollment. 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. If the patient has benefit after 2 years, the trial chair and the sponsor must be consulted to evaluate how to continue with the treatment.

Group Type: EXPERIMENTAL

Bintrafusp alfa

Intervention Type: DRUG

Bintrafusp alfa (M7824) is a bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β) receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 antibody blocking programmed death-ligand 1 (PD-L1).

Day 1 of week 1 of treatment will start within 1-5 days from enrollment. Cycles will be administered every 2 weeks (±3 days) until progression or other reason to discontinue. If a pseudoprogression is suspected patient is allowed to continue treatment until loss of clinical benefit as judged by principal investigator and after the permission from the trial chair is granted.

On Day 1 of each cycle (QW2), all eligible patients will receive:

Bintrafusp alfa (M7824): 1200mg, IV infusion over 60 minutes Current experience revealed that IRRs to bintrafusp alfa occur seldomly and are generally mild to moderate in severity. Therefore, administration of a premedication is generally not required.

Interventions

Bintrafusp alfa

Bintrafusp alfa (M7824) is a bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β) receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 antibody blocking programmed death-ligand 1 (PD-L1).

Day 1 of week 1 of treatment will start within 1-5 days from enrollment. Cycles will be administered every 2 weeks (±3 days) until progression or other reason to discontinue. If a pseudoprogression is suspected patient is allowed to continue treatment until loss of clinical benefit as judged by principal investigator and after the permission from the trial chair is granted.

On Day 1 of each cycle (QW2), all eligible patients will receive:

Bintrafusp alfa (M7824): 1200mg, IV infusion over 60 minutes Current experience revealed that IRRs to bintrafusp alfa occur seldomly and are generally mild to moderate in severity. Therefore, administration of a premedication is generally not required.

Intervention Type: DRUG

Other Intervention Names

M7824

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación GECP

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mariano Provencio, MD

Role: PRINCIPAL_INVESTIGATOR

Fundación GECP President

Locations

Hospital General Universitario de Alicante

Alicante, Alicante, Spain

ICO Badalona, Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Universitari Vall d' Hebron

Barcelona, Barcelona, Spain

Hospital Parc Taulí

Barcelona, Barcelona, Spain

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital de Basurto

Bilbao, Bilbao, Spain

ICO Girona, Hospital Josep Trueta

Girona, Girona, Spain

Hospitalario Universitario A Coruña

A Coruña, La Coruña, Spain

Hospital Universitario Lucus Augusti

Lugo, Lugo, Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, Spain

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Hospital Universitario Virgen De La Victoria

Málaga, Málaga, Spain

Hospital Universitario Central de Asturias

Oviedo, Oviedo, Spain

Hospital Clínico de Valencia

Valencia, Valencia, Spain

Hospital Clínico Universitario de Valladolid

Valladolid, Valladolid, Spain

Countries

Spain

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.gecp.org

Web page of the sponsor where users can find more information about Fundación GECP studies

Other Identifiers

2020-004902-67

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GECP 20/09_BIMES

Identifier Type: -

Identifier Source: org_study_id