MSB0011359C (M7824) in Metastatic or Locally Advanced Solid Tumors
A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, PK, Biological and Clinical Activity of MSB0011359C in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications
2 other identifiers
interventional
600
12 countries
118
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2015
Longer than P75 for phase_1
118 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 30, 2015
CompletedFirst Posted
Study publicly available on registry
August 7, 2015
CompletedStudy Start
First participant enrolled
August 31, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 23, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
May 23, 2022
CompletedResults Posted
Study results publicly available
May 3, 2024
CompletedMay 3, 2024
November 1, 2023
6.7 years
July 30, 2015
November 6, 2023
November 6, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Adverse event (AE): any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.
From start of study drug administration up to 139 weeks
Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death
Treatment-related TEAEs are any untoward medical occurrence in a participant who received study drug with causal relationship with the investigational product as assessed by the investigator. Related TEAEs were events with relationship missing, unknown or yes. Number of participants With treatment-related TEAEs, treatment-related serious TEAEs and treatment-related TEAE leading to death were reported.
From start of study drug administration up to 139 weeks
Number of Participants With TEAEs and Related TEAEs Based on Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03
AEs were graded according to severity using NCI-CTCAE Version 4.03. Severity of TEAEs were graded as Grade 1: mild (not causing any significant problem, dose adjustment not required), Grade 2: moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event), Grade 3: Severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event), Grade 4: Life-threatening, Grade 5: Death. Number of Participants with TEAEs and Related TEAEs Based on Severity having Grade greater than or equal to (\>=) 3 and Grade \>=4 were reported.
From start of study drug administration up to 139 weeks
Dose-escalation: Number of Participants With Dose-Limiting Toxicities According to the National Cancer Institute Common Terminology Criteria For Adverse Events(NCI-CTCAE), v4.03
A DLT was defined as any grade \>= 3 Adverse Event (AE) suspected to be related to IMP by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment. According to the NCI-CTCAE, v4.03, occurring in the DLT evaluation period and assessed to be related to study treatment by the Investigator and / or Sponsor confirmed by the safety monitoring committee to be relevant for the study treatment.
From start of study drug administration up to 21 days
Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC)
BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Independent Endpoint Review Committee (IRC). BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.
From date of randomization up to Week 66
Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma
DCR is defined as the percentage of participants with a confirmed CR+PR+SD+ Non-CR/non-PD at any time as per RANO criteria. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the RANO criteria. CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.
From date of randomization up to Week 66
Secondary Outcomes (10)
Maximum Concentration (Cmax) of M7824 in Plasma
0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824
0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose post-dose
Apparent Terminal Half Life (t1/2) of M7824
Pre-dose, 0, 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Trough Plasma Concentration (Ctrough) of M7824
0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Apparent Plasma Clearance (CL) of M7824
0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
- +5 more secondary outcomes
Study Arms (1)
MSB0011359C (M7824)
EXPERIMENTALInterventions
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (118)
Arizona Clinical Research Center
Tucson, Arizona, 85715, United States
Pacific Oncology Associates
Escondido, California, 92025, United States
University of California Davis Health System
Sacramento, California, 95817, United States
California Pacific Medical Center
San Francisco, California, 94118, United States
Innovative Clinical Research Institute
Whittier, California, 90603, United States
Rocky Mountain Cancer Centers, LLP
Denver, Colorado, 80218, United States
Eastern Connecticut Hematology/Oncology Assoc.
Norwich, Connecticut, 06360, United States
Sylvester Cancer Center
Miami, Florida, 33136, United States
Hematology - Oncology Associates of Treasure Coast
Port Saint Lucie, Florida, 34952, United States
University Cancer & Blood Center, LLC
Athens, Georgia, 30607, United States
Southeastern Regional Medical Center
Newnan, Georgia, 30265, United States
Metairie Oncologists, LLC
Metairie, Louisiana, 70006, United States
National Cancer Institute
Bethesda, Maryland, 20892, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Michigan State University
Lansing, Michigan, 48910, United States
Washington University
St Louis, Missouri, 63110, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
UC Health Clinical Trials Office
Cincinnati, Ohio, 45206, United States
Case Comprehensive Cancer Center
Cleveland, Ohio, 44106, United States
Penn State University Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Greenville Hospital System University Medical Center (ITOR)
Greenville, South Carolina, 29605, United States
Tennessee Cancer Specialists
Knoxville, Tennessee, 37909, United States
Texas Oncology, P.A. - Austin
Austin, Texas, 78705, United States
Mary Crowley Cancer Research Centers
Dallas, Texas, 75230, United States
Texas Oncology, P.A. - Fort Worth
Fort Worth, Texas, 76104, United States
Oncology Consultants, P.A.
Houston, Texas, 77030, United States
University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics
Houston, Texas, 77030, United States
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229, United States
Texas Oncology, P.A. - Tyler
Tyler, Texas, 75702, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031, United States
Virginia Oncology Associates - Hampton
Norfolk, Virginia, 23502, United States
Compass Oncology
Vancouver, Washington, 98684, United States
Blacktown Hospital
Blacktown, New South Wales, 2148, Australia
St George Hospital
Kogarah, New South Wales, 2217, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
Port Macquarie Base Hospital
Port Macquarie, New South Wales, 2444, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Calvary Mater Newcastle
Waratah, New South Wales, 2298, Australia
Gallipoli Medical Research Foundation Ltd
Greenslopes, Queensland, 4120, Australia
Tasman Oncology Research Ltd
Southport, Queensland, 4216, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011, Australia
Peter MacCallum Cancer Centre-East Melbourne
East Melbourne, Victoria, 3002, Australia
Cabrini Hospital Malvern
Malvern, Victoria, 3144, Australia
Border Medical Oncology Research Unit
Wodonga, Victoria, 3690, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, 6150, Australia
Linear Clinical Research Limited
Nedlands, Western Australia, 6009, Australia
Institut Jules Bordet
Brussels, 1000, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
Grand Hôpital de Charleroi
Charleroi, 6000, Belgium
UZ Antwerpen
Edegem, 2650, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
Centre Hospitalier de l'Ardenne
Libramont, 6800, Belgium
C. H. U. Sart Tilman
Liège, 4000, Belgium
GZA Ziekenhuizen - Campus Sint-Augustinus
Wilrijk, 2610, Belgium
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
Centre Antoine Lacassagne
Nice, Alpes Maritimes, 06189, France
Centre Paul Strauss
Strasbourg, Bas Rhin, 67000, France
Hôpital de la Timone#
Marseille, Bouches-du-Rhône, 13385, France
Centre Georges François Leclerc
Dijon, Côte-d'Or, 21079, France
CHU Bordeaux - Hôpital Saint André
Bordeaux, Gironde, 33075, France
Institut Claudius Regaud-Oncopole
Toulouse, Haute Garonne, 31059, France
CHU de Grenoble - Hôpital Nord
Grenoble, Isere, 38043, France
ICO - Site René Gauducheau
Saint-Herblain, Loire Atlantique, 44805, France
Centre Oscar Lambret
Lille, Nord, 59020, France
Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris
Paris, Paris, 75248, France
Hôpital Saint-Louis
Paris, Paris, 75475, France
Groupe Hospitalier Pitie-Salpetriere
Paris, Paris, 75571, France
Centre Léon Bérard
Lyon, Rhone, 69008, France
Centre Hospitalier de la Croix Rousse
Lyon, Rhone, 69317, France
Hôpital Henri Mondor
Créteil, Val De Marne, 94010, France
Institut Régional du Cancer de Montpellier
Montpellier, 34298, France
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625, Germany
Cellex Koeln
Cologne, North Rhine-Westphalia, 50670, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
Dresden, Saxony, 01307, Germany
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
Berlin, 10117, Germany
Fondazione del Piemonte per l'Oncologia IRCC Candiolo
Candiolo, Torino, 10060, Italy
Ospedale San Raffaele
Milan, 20132, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133, Italy
IEO Istituto Europeo di Oncologia
Milan, 20141, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli, 80131, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126, Italy
Policlinico Universitario Agostino Gemelli
Roma, 00168, Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, 53100, Italy
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577, Japan
Kindai University Hospital
Osakasayama-shi, Osaka, 589-8511, Japan
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620, South Korea
Chungbuk National University Hospital
Cheongju-si, North Chungcheong, 28644, South Korea
Pusan National University Hospital
Busan, 49241, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 135-710, South Korea
Hospital Infanta Cristina
Badajoz, 06080, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinic i Provincial de Barcelona
Barcelona, 08036, Spain
Hospital General Universitario Gregorio Marañon
Madrid, 28007, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Centro Integral Oncologico Clara Campal
Madrid, 28050, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Hospital Universitario Virgen del Rocio
Seville, 41013, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Hospital Universitari i Politecnic La Fe
Valencia, 46026, Spain
National Taiwan University Hospital
Taipei, 100, Taiwan
Mackay Memorial Hospital
Taipei, 104, Taiwan
Taipei Medical University Hospital
Taipei, 110, Taiwan
Guy's Hospital
London, Greater London, SE1 9RT, United Kingdom
University College London Hospitals
London, Greater London, WC1E 6AG, United Kingdom
The Christie
Manchester, Greater Manchester, M20 4BX, United Kingdom
Southampton General Hospital
Southampton, Hampshire, SO16 6YD, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Strathclyde, G12 OYN, United Kingdom
Northern Centre for Cancer Care
Newcastle upon Tyne, Tyne & Wear, NE7 7DN, United Kingdom
Queen Elizabeth Hospital
Birmingham, West Midlands, B15 2TG, United Kingdom
Related Publications (8)
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.
PMID: 33323462RESULTCho BC, Daste A, Ravaud A, Salas S, Isambert N, McClay E, Awada A, Borel C, Ojalvo LS, Helwig C, Rolfe PA, Gulley JL, Penel N. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort. J Immunother Cancer. 2020 Jul;8(2):e000664. doi: 10.1136/jitc-2020-000664.
PMID: 32641320RESULTWilkins JJ, Vugmeyster Y, Dussault I, Girard P, Khandelwal A. Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. Adv Ther. 2019 Sep;36(9):2414-2433. doi: 10.1007/s12325-019-01018-0. Epub 2019 Jul 5.
PMID: 31278692RESULTStrauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL. Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFbeta, in Advanced Solid Tumors. Clin Cancer Res. 2018 Mar 15;24(6):1287-1295. doi: 10.1158/1078-0432.CCR-17-2653. Epub 2018 Jan 3.
PMID: 29298798RESULTTan 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.
PMID: 34009501RESULTRajan 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.
PMID: 38485188DERIVEDSpira 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.
PMID: 36568239DERIVEDVugmeyster 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.
PMID: 36066618DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Communication Center
- Organization
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study Officials
- STUDY DIRECTOR
Medical Responsible
EMD Serono Research & Development Institute, Inc, an affiliate of MerckKGaA, Darmstadt, Germany
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 30, 2015
First Posted
August 7, 2015
Study Start
August 31, 2015
Primary Completion
May 23, 2022
Study Completion
May 23, 2022
Last Updated
May 3, 2024
Results First Posted
May 3, 2024
Record last verified: 2023-11