A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma

NCT04501094 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 20014220-C-0142
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Metastatic urothelial carcinoma is lethal and has no cure. Response rates to current treatments are modest. Researchers want to find new strategies to treat the disease. In this study, they will test a drug called Bintrafusp alfa (M7824). The drug is a new immunotherapy that blocks the pathways that cancer cells use to stop the immune system from fighting cancer. Objective: To learn if M7824 can help the immune system's ability to fight urothelial cancer. Eligibility: People age 18 and older who have urothelial cancer that has spread to other parts of their body and they have been previously treated with chemotherapy or immunotherapy Design: Participants will be screened with a medical history and physical exam. They will have blood and urine tests. They will have imaging scans. They will have an electrocardiogram to measure heart function. Their ability to perform their normal activities will be evaluated. They may have a tumor biopsy. They will take a pregnancy test if needed. Participants will repeat some of the screening tests during the study. Treatment will be given in a series of 28-day cycles. Participants will get M7824 once every 2 weeks. It is given through an intravenous infusion. For this, a small plastic tube is put into an arm vein. They will get M7824 until their disease gets worse, they have unacceptable side effects, or they decide to stop treatment. Participants will have a follow-up visit 30 days after treatment ends. Then they will be followed every 12 weeks in the clinic or by telephone/email. Follow-up will last indefinitely.

Conditions

Urothelial Cancer

Keywords

TGF-Beta; Immune Therapy; PD-L1; Immunocytokine

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With an Objective Response Rate (ORR)

  The proportion of evaluable patients with objective response rate (ORR) defined as a partial response (PR) or complete response (CR) at the end of treatment with Bintrafusp alfa (M7824). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete response is disappearance of all target lesions.

  From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, approximately 3 months.

Secondary Outcomes (3)

• Number of Participants With Toxicity Grade >1

  Until confirmed progression, unacceptable toxicity or trial withdrawal, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.

• Number of Participants With Progression Free Survival (PFS)

  From start of treatment to time of progression or death, approximately 6 weeks (first scheduled restaging scan)

• Number of Participants That Survived

  Time from treatment to the date of death from any cause, approximately 11 months.

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Date treatment consent signed to date off study, approximately 4 months and 3 days for cohort 1B and 11 months and 17 days for cohort B.

Study Arms (1)

1/Arm 1-Treatment with Bintrafusp alfa (M7824)

EXPERIMENTAL

Treatment with Bintrafusp alfa (M7824)

Drug: Bintrafusp alfa (M7824)

Interventions

Bintrafusp alfa (M7824) DRUG

1200 mg administered intravenous (IV) every two weeks

Also known as: M7824

1/Arm 1-Treatment with Bintrafusp alfa (M7824)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.
• Male or female patients aged greater than or equal to 18 years of age at time of consent.
• Patients with histologically confirmed diagnosis of urothelial carcinoma of the urinary tract, including the renal pelvis, ureter, bladder, or urethra. Differentiation with variant histologies (e.g. squamous cell differentiated) will be permitted. Mixed histologies are required to have a dominant urothelial/transitional cell pattern.
• Patients must have metastatic disease defined as new or progressive lesions on cross- sectional imaging. Radiological evaluation should occur within 21 days prior to enrollment.
• Patient must have evaluable and measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Patients may have been previously treated with prior cytotoxic chemotherapy regimen or targeted agent. Patients may have received any number of prior cytotoxic agents.
• Patients may have had prior immunomodulating therapy including therapy targeting the Programmed death-1 (PD-1)/Programmed Cell Death Ligand 1 (PD-L1 axis (cohort 2A and B) but excluding prior treatment with Bintrafusp Alfa (M7824).
• Pre-treatment tissue biopsy and/or archival tissue availability for PD-L1 expression testing is mandatory for enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
• Required laboratory values reflective of organ function are listed below:
• Absolute neutrophil count greater than or equal to 1000/microliter
• Platelets greater than or equal to 75,000 microliter
• Hemoglobin greater than or equal to 9 g/dL (erythrocyte transfusions are allowed to achieve acceptable Hgb)
• Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT)/Serum glutamic-pyruvic transaminase (SGPT) less than or equal to 1.5 institutional upper limit of normal (ULN) with the following exception:
• Patients with liver involvement who have AST and ALT less than or equal to 5 ULN may be enrolled.

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to M7824 investigational agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Symptomatic central nervous system metastasis.
• Subjects unwilling to accept blood products as medically indicated
• Pregnant women are excluded from this study because M7824 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M7824, breastfeeding should be discontinued if the mother is treated with these agents.
• Patients with any active or recent history of a known or suspected autoimmune disease (with the exception of diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment) or recent history of a syndrome that required treatment with either systemic corticosteroids (\>10 mg daily prednisone equivalent) or immunosuppressive medications. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Patients with a currently active second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ or incidental organ-confined prostate cancer found on cystoprostatectomy (provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score \<= 3+4, prostate-specific antigen (PSA) undetectable). Patients are not considered to have a currently active malignancy if they have completed therapy and are free of disease for \>= 2 years and currently do not require systemic therapy.
• Patients who have received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted.
• Patients having tumor lesion(s) in the liver or chest which are 10 cm or larger.
• Patients previously treated with M7824.
• Patients previously treated with PD-1/PD-L1 checkpoint inhibitors (for Cohorts 1A and 1B only)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Camurati-Engelmann Syndrome

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dr. Andrea B. Apolo
• Organization: National Cancer Institute

andrea.apolo@nih.gov

301-480-0536

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 6, 2020
• Study Start: October 26, 2020
• Primary Completion: January 19, 2021
• Study Completion: October 13, 2021
• Last Updated: March 22, 2022
• Results First Posted: March 22, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)