Ignite Creation Date:
2025-12-25 @ 1:38 AM
Ignite Modification Date:
2025-12-27 @ 11:04 AM
Study NCT ID:
NCT04501094
Status:
TERMINATED
Last Update Posted:
2022-03-22
First Post:
2020-08-05
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma
Status:
TERMINATED
Status Verified Date:
2022-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Because of the low accrual and the safety concerns we closed the study.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
Detailed Description:
Background:
* Metastatic urothelial carcinoma is lethal and incurable with a median overall survival of 14 months from diagnosis.
* Immune checkpoint inhibitors targeting the Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have greatly changed clinical management of metastatic urothelial carcinoma (mUC) improving survival by 3 months in the second-line setting.
* Five PD-1/PD-L1 inhibitors are Food and Drug Administration (FDA)-approved for for second-line metastatic urothelial carcinoma (mUC), two agents for first-line cisplatin-ineligible mUC. However, response rates are modest, ranging from15-20% in the second-line and 24% in the first-line cisplatin-ineligible.
* Therefore, novel strategies are needed to extend benefit of immunotherapy to the remaining approximately 75% of non-responders.
* Higher levels of transforming growth factor-beta (TGF-beta) are associated with immune escape, therapy resistance and poor outcomes in advanced malignancies. Non-responders to anti-PD-1/PD-L1 antibodies have also been found to have increased TGF-beta in the tumor microenvironment.
* Bintrafusp alfa (M7824) is a novel first-in-class bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused to the extracellular domain of human TGF-beta receptor II (TGFbetaRII), which effectively functions to sequester or "trap" all three TGF-beta isoforms. A phase I study of M7824 (NCT02517398) demonstrated a manageable safety profile and clinical efficacy among patients with heavily pre-treated advanced solid tumors.
* We hypothesize that M7824 is safe and improves outcomes in patients with checkpoint naive or refractory urothelial carcinoma.
Objectives:
-To evaluate the activity of M7824 as determined by objective response rate (ORR) in two metastatic urothelial carcinoma cohorts:
* Cohort 1: Checkpoint inhibitor naive
* Cohort 1A: cisplatin ineligible
* Cohort 1B: refractory post-platinum therapy
* Cohort 2: Checkpoint inhibitor previously treated patients
* Cohort 2A: previously achieved a Complete Response (CR)/Partial Response (PR)
* Cohort 2B: previously had Stable Disease (SD)/Progressive Disease (PD)
Eligibility:
* Patients must have a histologically confirmed diagnosis of metastatic urothelial cancer.
* Patients may have been previously treated with prior cytotoxic chemotherapy regimen or targeted agent. Patients may have received any number of prior cytotoxic agents.
* 18 years of age or older
Design:
* This is an open label, non-randomized, single arm phase II trial of M7824 in checkpoint inhibitor naive and previously treated patients with urothelial carcinoma of the bladder.
* M7824 (intravenous 1200 mg fixed dose) will be delivered every 2 weeks
* Patients will receive treatment in cycles consisting of 4 weeks.
* A maximum of 75 subjects will be enrolled in this trial.
* Metastatic urothelial carcinoma is lethal and incurable with a median overall survival of 14 months from diagnosis.
* Immune checkpoint inhibitors targeting the Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have greatly changed clinical management of metastatic urothelial carcinoma (mUC) improving survival by 3 months in the second-line setting.
* Five PD-1/PD-L1 inhibitors are Food and Drug Administration (FDA)-approved for for second-line metastatic urothelial carcinoma (mUC), two agents for first-line cisplatin-ineligible mUC. However, response rates are modest, ranging from15-20% in the second-line and 24% in the first-line cisplatin-ineligible.
* Therefore, novel strategies are needed to extend benefit of immunotherapy to the remaining approximately 75% of non-responders.
* Higher levels of transforming growth factor-beta (TGF-beta) are associated with immune escape, therapy resistance and poor outcomes in advanced malignancies. Non-responders to anti-PD-1/PD-L1 antibodies have also been found to have increased TGF-beta in the tumor microenvironment.
* Bintrafusp alfa (M7824) is a novel first-in-class bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused to the extracellular domain of human TGF-beta receptor II (TGFbetaRII), which effectively functions to sequester or "trap" all three TGF-beta isoforms. A phase I study of M7824 (NCT02517398) demonstrated a manageable safety profile and clinical efficacy among patients with heavily pre-treated advanced solid tumors.
* We hypothesize that M7824 is safe and improves outcomes in patients with checkpoint naive or refractory urothelial carcinoma.
Objectives:
-To evaluate the activity of M7824 as determined by objective response rate (ORR) in two metastatic urothelial carcinoma cohorts:
* Cohort 1: Checkpoint inhibitor naive
* Cohort 1A: cisplatin ineligible
* Cohort 1B: refractory post-platinum therapy
* Cohort 2: Checkpoint inhibitor previously treated patients
* Cohort 2A: previously achieved a Complete Response (CR)/Partial Response (PR)
* Cohort 2B: previously had Stable Disease (SD)/Progressive Disease (PD)
Eligibility:
* Patients must have a histologically confirmed diagnosis of metastatic urothelial cancer.
* Patients may have been previously treated with prior cytotoxic chemotherapy regimen or targeted agent. Patients may have received any number of prior cytotoxic agents.
* 18 years of age or older
Design:
* This is an open label, non-randomized, single arm phase II trial of M7824 in checkpoint inhibitor naive and previously treated patients with urothelial carcinoma of the bladder.
* M7824 (intravenous 1200 mg fixed dose) will be delivered every 2 weeks
* Patients will receive treatment in cycles consisting of 4 weeks.
* A maximum of 75 subjects will be enrolled in this trial.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 20-C-0142 | None | None | View |