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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: MSB0011359C

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.

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Port Macquarie, New South Wales, Australia, 2444
      • Port Macquarie Base Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Gallipoli Medical Research Foundation Ltd
    • Southport, Queensland, Australia, 4216
      • Tasman Oncology Research Ltd
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre-East Melbourne
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital Malvern
    • Wodonga, Victoria, Australia, 3690
      • Border Medical Oncology Research Unit
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Limited
• Belgium
  • Bruxelles, Belgium, 1000
    • Institut Jules Bordet
  • Bruxelles, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Charleroi, Belgium, 6000
    • Grand Hôpital de Charleroi
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Libramont, Belgium, 6800
    • Centre Hospitalier de l'Ardenne
  • Liège, Belgium, 4000
    • C. H. U. Sart Tilman
  • Wilrijk, Belgium, 2610
    • GZA Ziekenhuizen - campus Sint-Augustinus
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
• France
  • Montpellier, France, 34298
    • Institut régional du Cancer de Montpellier
  • Alpes Maritimes
    • Nice cedex 02, Alpes Maritimes, France, 06189
      • Centre Antoine Lacassagne
  • Bas Rhin
    • Strasbourg Cedex, Bas Rhin, France, 67000
      • Centre Paul Strauss
  • Bouches-du-Rhône
    • Marseille cedex 5, Bouches-du-Rhône, France, 13385
      • Hôpital de la Timone#
  • Côte-d'Or
    • Dijon cedex, Côte-d'Or, France, 21079
      • Centre Georges François Leclerc
  • Gironde
    • Bordeaux cedex, Gironde, France, 33075
      • CHU Bordeaux - Hôpital Saint André
  • Haute Garonne
    • Toulouse cedex 09, Haute Garonne, France, 31059
      • Institut Claudius Regaud-Oncopole
  • Isere
    • Grenoble cedex 9, Isere, France, 38043
      • CHU de Grenoble - Hôpital Nord
  • Loire Atlantique
    • Saint Herblain, Loire Atlantique, France, 44805
      • Ico - Site René Gauducheau
  • Nord
    • Lille cedex, Nord, France, 59020
      • Centre Oscar Lambret
  • Paris
    • Paris Cedex 05, Paris, France, 75248
      • Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris
    • Paris Cedex 10, Paris, France, 75475
      • Hôpital Saint-Louis
    • Paris cedex 12, Paris, France, 75571
      • Groupe Hospitalier Pitie-Salpetriere
  • Rhone
    • Lyon, Rhone, France, 69008
      • Centre Leon Berard
    • Lyon Cedex 04, Rhone, France, 69317
      • Centre Hospitalier de la Croix Rousse
  • Val De Marne
    • Créteil Cedex, Val De Marne, France, 94010
      • Hôpital Henri Mondor
• Germany
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover
  • Nordrhein Westfalen
    • Koeln, Nordrhein Westfalen, Germany, 50670
      • Cellex Koeln
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus TU Dresden
• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano, Italy, 20141
    • IEO Istituto Europeo di Oncologia
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione G. Pascale
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli
  • Siena, Italy, 53100
    • A.O.U. Senese Policlinico Santa Maria alle Scotte
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Fondazione del Piemonte per l'Oncologia IRCC Candiolo
• Japan
  • Chiba-Ken
    • Kashiwa-shi, Chiba-Ken, Japan, 277-8577
      • National Cancer Center Hospital East
  • Osaka-Fu
    • Osakasayama-shi, Osaka-Fu, Japan, 589-8511
      • Kindai University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Chungcheongbuk-do
    • Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 28644
      • Chungbuk National University Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
• Spain
  • Badajoz, Spain, 06080
    • Hospital Infanta Cristina
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebrón
  • Barcelona, Spain, 08036
    • Hospital Clínic I Provincial de Barcelona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 104
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 110
    • Taipei Medical University Hospital
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, WC1E 6AG
      • University College London Hospitals
    • London, Greater London, United Kingdom, SE1 9RT
      • Guy's Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • The Christie
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom, G12 OYN
      • Beatson West of Scotland Cancer Centre
  • Tyne & Wear
    • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE7 7DN
      • Northern Centre for Cancer Care
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TG
      • Queen Elizabeth Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Arizona Clinical Research Center
  • California
    • Escondido, California, United States, 92025
      • Pacific Oncology Associates
    • Sacramento, California, United States, 95817
      • University of California Davis Health System
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers, LLP
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology/Oncology Assoc.
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Cancer Center
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology - Oncology Associates of Treasure Coast
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
    • Newnan, Georgia, United States, 30265
      • Southeastern Regional Medical Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Metairie Oncologists, LLC
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Lansing, Michigan, United States, 48910
      • Michigan State University
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45206
      • UC Health Clinical Trials Office
    • Cleveland, Ohio, United States, 44106
      • Case Comprehensive Cancer Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University Milton S. Hershey Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System University Medical Center (ITOR)
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialists
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology, P.A. - Austin
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Centers
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, P.A. - Fort Worth
    • Houston, Texas, United States, 77030
      • Oncology Consultants, P.A.
    • Houston, Texas, United States, 77030
      • University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC
    • Tyler, Texas, United States, 75702
      • Texas Oncology, P.A. - Tyler
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Hampton
  • Washington
    • Vancouver, Washington, United States, 98684
      • Compass Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Other protocol-defined inclusion criteria could apply.

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)

Other protocol-defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSB0011359C (M7824)	Drug: 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.; Other Names: M7824

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of M7824 in Plasma	Cmax was obtained directly from the concentration versus time curve.	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	Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).	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	Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (*) 2/ λz, where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Pre-dose, 0, 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Trough Plasma Concentration (Ctrough) of M7824	Ctrough is the plasma concentration of a drug prior to administration.	0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Apparent Plasma Clearance (CL) of M7824	CL is defined as the time it takes for the study drug to be completely removed from the body's plasma.	0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824	The detection of antibodies to M7824 was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive ADA of M7824 were reported.	Predose, up to Week 52
Number of Participants With Best Overall Response (BOR) as Assessed by Investigator	BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Investigator. 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: Number of Participants With TEAEs and Serious TEAEs	An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. TEAEs were defined as events with onset date or worsening during the on-treatment period. Serious Adverse Event (SAE) was 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. Any TEAE included participants with both serious and non-serious AEs.	From start of study drug administration up to 200 weeks
Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE 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 200 weeks
Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to 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 >= 3 and Grade >=4 TEAEs were reported.	From start of study drug administration up to 200 weeks

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc, an affiliate of MerckKGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• 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.
• Cho 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. Erratum In: J Immunother Cancer. 2020 Oct;8(2):
• Wilkins 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.
• Strauss 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.
• 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.
• 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.

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2015
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): May 23, 2022

Study Registration Dates

• First Submitted: July 30, 2015
• First Submitted That Met QC Criteria: August 4, 2015
• First Posted (Estimated): August 7, 2015

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Solid tumor; Bintrafusp alfa; INTR@PID; MSB0011359C (M7824); Metastatic or Locally Advanced Solid Tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: EMR 200647-001; 2015-004366-28 (EudraCT Number)