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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05005429
Recruitment Status : Recruiting
First Posted : August 13, 2021
Last Update Posted : June 2, 2022
Sponsor:
Information provided by (Responsible Party):
Fundación GECP

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.


Condition or disease Intervention/treatment Phase
Mesothelioma; Lung Drug: Bintrafusp alfa Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 20, 2021
Estimated Primary Completion Date : March 30, 2025
Estimated Study Completion Date : April 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: 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.

Drug: 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.

Other Name: M7824




Primary Outcome Measures :
  1. To evaluate the efficacy of the treatment [ Time Frame: From the date of randomization to the date of last follow up, assessed up to 24 months ]
    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.


Secondary Outcome Measures :
  1. To evaluate the Overall Response Rate (ORR) of the treatment [ Time Frame: From the date of randomization to the date of last follow up, assessed up to 24 months ]
    To evaluate the ORR of the treatment as measured by investigator-assessed overall response rate (ORR) according to RECIST v1.1.

  2. To evaluate the Overall survival (OS) rate [ Time Frame: From the date of randomization to the date of last follow up, assessed up to 24 months ]
    To evaluate the Overall survival (OS) rate at end the treatment. OS defined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.

  3. To determinate duration of response [ Time Frame: From the date of confirmed response to last follow up, assessed up to 24 months ]
    Duration of response is the time from response to progression or death

  4. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: From the subject's written consent to participate in the study through 30 days after the final administration of the drug ]
    Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05005429


Contacts
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Contact: Eva Pereira +34934302006 gecp@gecp.org

Locations
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Spain
ICO Badalona, Hospital Germans Trias i Pujol Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Marta Domenech, MD         
Principal Investigator: Marta Domenech, MD         
ICO Hospitalet Recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08908
Contact: Ernest Nadal, MD         
Principal Investigator: Ernest Nadal, MD         
Hospitalario Universitario A Coruña Recruiting
A Coruña, La Coruña, Spain, 15006
Contact: Rosario García Campelo, MD         
Principal Investigator: Rosario García Campelo, MD         
Hospital Universitario Puerta de Hierro Recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Mariano Provencio, MD         
Principal Investigator: Mariano Provencio, MD         
Hospital General Universitario de Alicante Recruiting
Alicante, Spain, 03010
Contact: Bartomeu Massuti, MD         
Principal Investigator: Bartomeu Massuti, MD         
Hospital Universitari Vall d' Hebron Recruiting
Barcelona, Spain, 08035
Contact: Susana Cedrés, MD         
Principal Investigator: Susana Cedrés, MD         
Hospital Parc Taulí Recruiting
Barcelona, Spain, 08208
Contact: Laia Vilà, MD         
Principal Investigator: Laia Vilà, MD         
Hospital de Basurto Recruiting
Bilbao, Spain, 48013
Contact: Mª Ángeles Sala, MD         
Principal Investigator: Mª Ángeles Sala, MD         
ICO Girona, Hospital Josep Trueta Recruiting
Girona, Spain, 17007
Contact: Elia Sais, MD         
Principal Investigator: Elia Sais, MD         
Hospital Universitario Lucus Augusti Recruiting
Lugo, Spain, 27003
Contact: Begoña Campos, MD         
Principal Investigator: Begoña Campos, MD         
Hospital Universitario Fundación Jiménez Díaz Recruiting
Madrid, Spain, 28040
Contact: Manuel Dómine, MD         
Principal Investigator: Manuel Dómine, MD         
Hospital Universitario Virgen De La Victoria Recruiting
Málaga, Spain, 29010
Contact: Jose Manuel Trigo, MD         
Principal Investigator: Jose Manuel Trigo, MD         
Hospital Universitario Central de Asturias Recruiting
Oviedo, Spain, 33011
Contact: Carlos Álvarez Fernández, MD         
Principal Investigator: Carlos Álvarez Fernández, MD         
Hospital Clínico de Valencia Recruiting
Valencia, Spain, 46010
Contact: Paloma Martín, MD         
Principal Investigator: Paloma Martín, MD         
Hospital Clínico Universitario de Valladolid Recruiting
Valladolid, Spain, 47003
Contact: Rafael López, MD         
Principal Investigator: Rafael López, MD         
Sponsors and Collaborators
Fundación GECP
Investigators
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Principal Investigator: Mariano Provencio, MD Fundación GECP President
Additional Information:
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Responsible Party: Fundación GECP
ClinicalTrials.gov Identifier: NCT05005429    
Other Study ID Numbers: GECP 20/09_BIMES
2020-004902-67 ( EudraCT Number )
First Posted: August 13, 2021    Key Record Dates
Last Update Posted: June 2, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación GECP:
Malignant pleural mesothelioma
Bintrafusp alfa
Additional relevant MeSH terms:
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Mesothelioma
Mesothelioma, Malignant
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