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

NCT05005429 | Completed Phase 2 Results DMC

• 2 other identifiers: GECP 20/09_BIMES2020-004902-67
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 15

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.

Conditions

Mesothelioma; Lung

Keywords

Malignant pleural mesothelioma; Bintrafusp alfa

Outcome Measures

Primary Outcomes (1)

• To Evaluate the Efficacy of the Treatment

  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. Progression is defined using Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 as an increase of at least 20%in the sumof thediameters of viable (enhancing) target lesions, taking as reference the smallest sumof thediameters of the viable (enhancing) target lesions. The sum must also demonstrate an absoluteincrease of at least 5 mm.

  From administration of first dose of bintrafusp alfa until objective tumor progression or death, up to 2 years.

Study Arms (1)

Experimental: Bintrafusp alfa (M7824)

EXPERIMENTAL

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.

Drug: Bintrafusp alfa

Interventions

Bintrafusp alfa 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.

Also known as: M7824

Experimental: Bintrafusp alfa (M7824)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 .

You may not qualify if:

• 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)

Sponsors & Collaborators

• Fundación GECP: lead

Study Sites (15)

Hospital General Universitario de Alicante

Alicante, Alicante, 03010, Spain

Location

ICO Badalona, Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitari Vall d' Hebron

Barcelona, Barcelona, 08035, Spain

Location

Hospital Parc Taulí

Barcelona, Barcelona, 08208, Spain

Location

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital de Basurto

Bilbao, Bilbao, 48013, Spain

Location

ICO Girona, Hospital Josep Trueta

Girona, Girona, 17007, Spain

Location

Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, Lugo, 27003, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Virgen De La Victoria

Málaga, Málaga, 29010, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Oviedo, 33011, Spain

Location

Hospital Clínico de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, Valladolid, 47003, Spain

Location

Related Links

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

MeSH Terms

Conditions

Mesothelioma; Mesothelioma, Malignant

Interventions

bintrafusp alfa protein, human

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

No study limitations

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

gecp@gecp.org

+34 934302006

Study Officials

• Mariano Provencio, MD

  Fundación GECP President

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: August 13, 2021
• Study Start: September 20, 2021
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2024
• Last Updated: December 23, 2025
• Results First Posted: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15)