A Study to Evaluate the Efficacy and Safety of Bintrafusp Alfa (M7824) Monotherapy in Metastatic or Locally Advanced Urothelial Cancer

A Phase Ib Trial to Evaluate the Efficacy and Safety of Bintrafusp Alfa Monotherapy in Metastatic or Locally Advanced/Unresectable Urothelial Cancer With Disease Progression or Recurrence Following Treatment With a Platinum Agent

The purpose of this study is to evaluate bintrafusp alfa in participants with metastatic or locally advanced urothelial cancer. This trial provides the first evaluation of bintrafusp alfa in participants with urothelial cancer that has progressed following platinum therapy.

Study Overview

• Status: Terminated
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Bintrafusp alfa

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
• France
  • Bordeaux, France, 33000
    • GSK Investigational Site
  • Poitiers Cedex, France, 86021
    • GSK Investigational Site
  • Toulouse Cedex 9, France, 31059
    • GSK Investigational Site
  • Villejuif Cedex, France, 94805
    • GSK Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Madrid, Spain, 28041
    • GSK Investigational Site
  • Madrid, Spain, 28040
    • GSK Investigational Site
  • Sevilla, Spain, 41013
    • GSK Investigational Site
• United States
  • New York
    • Lake Success, New York, United States, 11041
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants can give signed informed consent/assent.
• Participants with histologically confirmed locally advanced or metastatic or locally advanced/unresectable urothelial carcinoma (including renal, pelvis, ureter, urinary bladder, urethra).
• Able to provide, a tumor tissue sample collected during screening and prior to administration of bintrafusp alfa.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Participants with adequate organ system functions.
• Life expectancy of at least 12 weeks.
• A female is eligible if she is not pregnant or breastfeeding.

Exclusion Criteria:

• Active brain and/or leptomeningeal disease that is symptomatic or requires therapeutic intervention. Participants with asymptomatic central nervous system (CNS) metastases who are clinically stable as demonstrated by serial brain images and have no requirement for corticosteroids for at least 14 days prior to enrollment are eligible.
• History of malignancy other than urothelial cancer within the last 3 years except for localized tumors that have been treated with curative intent or have not required therapy in the past 2 years. (e.g., resected non-melanoma skin cancer).
• No more than 2 lines of systemic therapy for the treatment of metastastic disease. If the most recent therapy was not a platinum-based regimen, the participant must have progressed on or after that therapy.
• Cirrhosis or current unstable liver or biliary disease per investigator assessment.
• Current pneumonitis or history of non-infectious pneumonitis that required systemic immunosuppressive treatment.
• Active autoimmune disease that required systemic immunosuppressive treatment within the past 2 years.
• Received prior allogeneic/autologous bone marrow or solid organ transplant.
• Receiving systemic corticosteroids (>10 milligrams [mg] daily oral prednisone or equivalent) or other immunosuppressive agent within 7 days prior to study treatment. Inhaled or topical steroids are permitted.
• Known severe hypersensitivity reactions to monoclonal antibodies or any ingredient used in the study treatment formulation (Grade >=3 National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0).
• Active infection requiring systemic therapy.
• Received any live vaccine within 30 days prior first dose of intervention.
• Known history of positive test for human immunodeficiency virus (HIV) with the exception of participants with cluster of differentiation 4 (CD4) + T-cell (CD4+) counts >=350 cells per microliter (cells /uL) and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections.
• Active hepatitis B virus (HBV) (HBV surface antigen-positive).
• Active hepatitis C virus (HCV) infection, or positive HCV antibody, with the exception of participants that 1. Have HCV viral load below the limits of quantitation and 2. Completed curative antiviral therapy or are receiving and compliant with antiviral therapy.
• History or evidence of cardiac abnormalities within the 6 months prior to first dose of intervention.
• Participants with history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for investigational drug treatment are also excluded.
• Any other serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results.
• Received prior systemic anti-cancer therapy within 2 weeks prior to study treatment.
• Received prior therapy with an anti-programmed death 1 (PD-1), anti-programmed death Ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Received prior therapy targeting transforming growth factor (TGF) beta - (e.g., Galunistertib).
• Received radiation therapy (or other non-systemic disease therapy) within 2 weeks prior to study treatment.
• Undergone major surgery within 4 weeks prior to administration of study treatment.

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: Participants receiving bintrafusp alfa; Participants will receive bintrafusp alfa.	Drug: Bintrafusp alfa; Participants will receive bintrafusp alfa.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Overall Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	Confirmed overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm).	Up to approximately 22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. AEs which start or worsen on or after Bintrafusp alfa infusion are defined as treatment-emergent.	Up to approximately 22 months
Number of Participants With Worst Grade Treatment Emergent AEs	Treatment emergent adverse events were analyzed using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition. AEs which start or worsen on or after Bintrafusp alfa infusion are defined as treatment-emergent.	Up to approximately 22 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): August 15, 2022
• Study Completion (Actual): August 15, 2022

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: M7824; Urothelial Cancer; Response Evaluation Criteria in Solid Tumors; Bintrafusp Alfa; Platinum Agent
• Other Study ID Numbers: 213152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No