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

• ClinicalTrials.gov Identifier: NCT04349280
• Recruitment Status: Active, not recruiting
• First Posted: April 16, 2020
• Last Update Posted: September 23, 2022
• Sponsor: GlaxoSmithKline
• Collaborator: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Neoplasms	Drug: Bintrafusp alfa	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a single arm study.
• Masking: None (Open Label)
• Masking Description: This is an open label study.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 15, 2020
• Estimated Primary Completion Date: November 2, 2022
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Participants receiving bintrafusp alfa; Participants will receive bintrafusp alfa.	Drug: Bintrafusp alfa; Participants will receive bintrafusp alfa.

Outcome Measures

Primary Outcome Measures :

1. Confirmed overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 assessed by Investigator [ Time Frame: Up to 3 years ]

Secondary Outcome Measures :

1. Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 3 years ]
2. Number of participants with AEs by their severity [ Time Frame: Up to 3 years ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, New York

GSK Investigational Site

Lake Success, New York, United States, 11041

United States, Ohio

GSK Investigational Site

Cincinnati, Ohio, United States, 45229

GSK Investigational Site

Columbus, Ohio, United States, 43210

United States, Virginia

GSK Investigational Site

Fairfax, Virginia, United States, 22031

United States, Washington

GSK Investigational Site

Seattle, Washington, United States, 98109

Canada, Ontario

GSK Investigational Site

Toronto, Ontario, Canada, M5G 2M9

France

GSK Investigational Site

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

Netherlands

GSK Investigational Site

Amsterdam, Netherlands, 1066 CX

Spain

GSK Investigational Site

Barcelona, Spain, 08035

GSK Investigational Site

Madrid, Spain, 28040

GSK Investigational Site

Madrid, Spain, 28041

GSK Investigational Site

Sevilla, Spain, 41013

United Kingdom

GSK Investigational Site

London, United Kingdom, EC1A 7BE

Sponsors and Collaborators

GlaxoSmithKline

Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT04349280
• Other Study ID Numbers: 213152
• First Posted: April 16, 2020
• Last Update Posted: September 23, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• 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.
• 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.
• URL: http://clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Bintrafusp Alfa; Platinum Agent; Response Evaluation Criteria in Solid Tumors; Urothelial Cancer; M7824