MSB0011359C (M7824) in Metastatic or Locally Advanced Solid Tumors

NCT ID: NCT02517398

Last Updated: 2024-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2022-05-23

Brief Summary

The main purpose of this Phase I study was to test MSB0011359C (M7824) at different dose levels to see if it is safe and well tolerated when given once every 2 weeks. Phase I means the study drug has not previously been given to humans or has only been given to a limited number of people, although it has been extensively studied in animals. Based on this information, it is hoped to find out which dose could be best for the treatment of patients. There are two parts of this research study: a dose-escalation part and an expansion part. Dose escalation means that the first people taking part in the study will receive low doses of the study drug, and as more people take part, the additional participants will receive a higher dose. This is done to find the safest dose for the study drug. Expansion means that after the dose-escalation part of the study has looked at the safety and effectiveness of different doses, many more people will be invited to take part in the study and will receive the study drug at the safest dose. Additional purposes of the study are to find out whether the study drug has anti-cancer effects and how the study drug is processed by the body.

Detailed Description

This is a Phase I, open-label, dose-escalation trial with consecutive parallel-group expansion in selected solid tumor indications. The current trial wascomposed of a standard dose escalation "3 + 3" cohort design, for which 3 to 6 subjects will be enrolled at each dose level depending on the occurrence of dose limiting toxicities (DLTs), followed by a consecutive parallel-group expansion in selected solid tumor in dications. Cohorts of 3 subjects with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or standard therapy has failed, will receive MSB0011359C (M7824) at escalating dose levels. After determination of the Maximum tolerated dose (MTD), enrollment in several expansion cohorts will be opened to determine the safety, pharmacokinetic (PK) / Pharmacodynamic, and clinical activity of MSB0011359C (M7824). Subjects who have experienced a confirmed complete response (CR) should continue treatment through the end of 12 months, although additional treatment is possible. In the case of progressive disease (PD), subjects should continue treatment through their next tumor assessment. Additional indications will be planned based on emerging data in the field.

Conditions

Solid Tumors

Study Design

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

Study Groups

MSB0011359C (M7824)

Group Type: EXPERIMENTAL

MSB0011359C

Intervention Type: DRUG

Subjects would receive intravenous infusion of MSB0011359C once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.

Interventions

MSB0011359C

Subjects would receive intravenous infusion of MSB0011359C once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.

Intervention Type: DRUG

Other Intervention Names

M7824

Eligibility Criteria

Inclusion Criteria

• Ability to understand the purpose of the study, provide signed and dated informed consent, and able to comply with all procedures
• In Japan, if a subject is < 20 years, the written informed consent from his/her parent or guardian will be required in addition to the subject's written consent
• Male or female subjects aged greater than or equal to (>=) 18 years
• Life expectancy >= 12 weeks as judged by the Investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry
• Disease must be measurable with at least 1 uni dimensional measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Adequate hematological, hepatic and renal function as defined in the protocol
• Effective contraception for both male and female subjects if the risk of conception exists

Exclusion Criteria

• Concurrent treatment with non-permitted drugs and other interventions
• Anticancer treatment within 28 days before the start of trial treatment, for example cyto reductive therapy, radiotherapy (with the exception of palliative radiotherapy delivered in a normal organ-spearing technique), immune therapy, or cytokine therapy
• Major surgery within 28 days before the start of trial treatment (prior diagnostic biopsy is permitted)
• Systemic therapy with immunosuppressive agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment
• Previous malignant disease (other than the target malignancy to be investigated in this trial) within the last 3 years. Subjects with history of cervical carcinoma in situ, superficial or non invasive bladder cancer or basal cell or squamous cell cancer in situ previously treated with curative intent are NOT excluded. Subjects with other localized malignancies treated with curative intent need to be discussed with the Medical Monitor.
• Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures
• Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (eg, corneal transplant, hair transplant)

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

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Research & Development Institute, Inc, an affiliate of MerckKGaA, Darmstadt, Germany

Locations

Arizona Clinical Research Center

Tucson, Arizona, United States

Pacific Oncology Associates

Escondido, California, United States

University of California Davis Health System

Sacramento, California, United States

California Pacific Medical Center

San Francisco, California, United States

Innovative Clinical Research Institute

Whittier, California, United States

Rocky Mountain Cancer Centers, LLP

Denver, Colorado, United States

Eastern Connecticut Hematology/Oncology Assoc.

Norwich, Connecticut, United States

Sylvester Cancer Center

Miami, Florida, United States

Hematology - Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, United States

University Cancer & Blood Center, LLC

Athens, Georgia, United States

Southeastern Regional Medical Center

Newnan, Georgia, United States

Metairie Oncologists, LLC

Metairie, Louisiana, United States

National Cancer Institute

Bethesda, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Michigan State University

Lansing, Michigan, United States

Washington University

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

UC Health Clinical Trials Office

Cincinnati, Ohio, United States

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Penn State University Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Greenville Hospital System University Medical Center (ITOR)

Greenville, South Carolina, United States

Tennessee Cancer Specialists

Knoxville, Tennessee, United States

Texas Oncology, P.A. - Austin

Austin, Texas, United States

Mary Crowley Cancer Research Centers

Dallas, Texas, United States

Texas Oncology, P.A. - Fort Worth

Fort Worth, Texas, United States

Oncology Consultants, P.A.

Houston, Texas, United States

University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics

Houston, Texas, United States

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, United States

Texas Oncology, P.A. - Tyler

Tyler, Texas, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Virginia Oncology Associates - Hampton

Norfolk, Virginia, United States

Compass Oncology

Vancouver, Washington, United States

Blacktown Hospital

Blacktown, New South Wales, Australia

St George Hospital

Kogarah, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Gallipoli Medical Research Foundation Ltd

Greenslopes, Queensland, Australia

Tasman Oncology Research Ltd

Southport, Queensland, Australia

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Peter MacCallum Cancer Centre-East Melbourne

East Melbourne, Victoria, Australia

Cabrini Hospital Malvern

Malvern, Victoria, Australia

Border Medical Oncology Research Unit

Wodonga, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Linear Clinical Research Limited

Nedlands, Western Australia, Australia

Institut Jules Bordet

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Grand Hôpital de Charleroi

Charleroi, , Belgium

UZ Antwerpen

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Centre Hospitalier de l'Ardenne

Libramont, , Belgium

C. H. U. Sart Tilman

Liège, , Belgium

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, , Belgium

Cross Cancer Institute

Edmonton, Alberta, Canada

Centre Antoine Lacassagne

Nice, Alpes Maritimes, France

Centre Paul Strauss

Strasbourg, Bas Rhin, France

Hôpital de la Timone#

Marseille, Bouches-du-Rhône, France

Centre Georges François Leclerc

Dijon, Côte-d'Or, France

CHU Bordeaux - Hôpital Saint André

Bordeaux, Gironde, France

Institut Claudius Regaud-Oncopole

Toulouse, Haute Garonne, France

CHU de Grenoble - Hôpital Nord

Grenoble, Isere, France

ICO - Site René Gauducheau

Saint-Herblain, Loire Atlantique, France

Centre Oscar Lambret

Lille, Nord, France

Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris

Paris, Paris, France

Hôpital Saint-Louis

Paris, Paris, France

Groupe Hospitalier Pitie-Salpetriere

Paris, Paris, France

Centre Léon Bérard

Lyon, Rhone, France

Centre Hospitalier de la Croix Rousse

Lyon, Rhone, France

Hôpital Henri Mondor

Créteil, Val De Marne, France

Institut Régional du Cancer de Montpellier

Montpellier, , France

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Cellex Koeln

Cologne, North Rhine-Westphalia, Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, Germany

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, , Germany

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, Italy

Ospedale San Raffaele

Milan, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

IEO Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Policlinico Universitario Agostino Gemelli

Roma, , Italy

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, , Italy

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Kindai University Hospital

Osakasayama-shi, Osaka, Japan

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, South Korea

Pusan National University Hospital

Busan, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital Infanta Cristina

Badajoz, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario Clinico San Carlos

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

National Taiwan University Hospital

Taipei, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

Taipei Medical University Hospital

Taipei, , Taiwan

Guy's Hospital

London, Greater London, United Kingdom

University College London Hospitals

London, Greater London, United Kingdom

The Christie

Manchester, Greater Manchester, United Kingdom

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, Strathclyde, United Kingdom

Northern Centre for Cancer Care

Newcastle upon Tyne, Tyne & Wear, United Kingdom

Queen Elizabeth Hospital

Birmingham, West Midlands, United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Italy; Japan; South Korea; Spain; Taiwan; United Kingdom

References

Strauss J, Gatti-Mays ME, Cho BC, Hill A, Salas S, McClay E, Redman JM, Sater HA, Donahue RN, Jochems C, Lamping E, Burmeister A, Marte JL, Cordes LM, Bilusic M, Karzai F, Ojalvo LS, Jehl G, Rolfe PA, Hinrichs CS, Madan RA, Schlom J, Gulley JL. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with human papillomavirus-associated malignancies. J Immunother Cancer. 2020 Dec;8(2):e001395. doi: 10.1136/jitc-2020-001395.

Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Tan B, Khattak A, Felip E, Kelly K, Rich P, Wang D, Helwig C, Dussault I, Ojalvo LS, Isambert N. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-beta and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. Target Oncol. 2021 Jul;16(4):435-446. doi: 10.1007/s11523-021-00809-2. Epub 2021 May 19.

Reference Type: RESULT

PMID: 34009501 (View on PubMed)

Rajan A, Abdul Sater H, Rahma O, Agajanian R, Lassoued W, Marte JL, Tsai YT, Donahue RN, Lamping E, Bailey S, Weisman A, Walter-Rodriguez B, Ito R, Vugmeyster Y, Sato M, Machl A, Schlom J, Gulley JL. Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with advanced non-small cell lung cancer. J Immunother Cancer. 2024 Mar 13;12(3):e008480. doi: 10.1136/jitc-2023-008480.

Reference Type: DERIVED

PMID: 38485188 (View on PubMed)

Spira A, Awada A, Isambert N, Lorente D, Penel N, Zhang Y, Ojalvo LS, Hicking C, Rolfe PA, Ihling C, Dussault I, Locke G, Borel C. Identification of HMGA2 as a predictive biomarker of response to bintrafusp alfa in a phase 1 trial in patients with advanced triple-negative breast cancer. Front Oncol. 2022 Dec 8;12:981940. doi: 10.3389/fonc.2022.981940. eCollection 2022.

Reference Type: DERIVED

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Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6.

Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=EMR%20200647-001

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

2015-004366-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR 200647-001

Identifier Type: -

Identifier Source: org_study_id