Ignite Creation Date:
2025-12-25 @ 2:16 AM
Ignite Modification Date:
2025-12-27 @ 11:00 PM
Study NCT ID:
NCT04417660
Status:
RECRUITING
Last Update Posted:
2025-09-19
First Post:
2020-06-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Bintrafusp Alfa (M7824) in Subjects With Thymoma and Thymic Carcinoma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase II, Open-Label Trial of Bintrafusp Alfa (M7824) in Subjects With Thymoma and Thymic Carcinoma
Status:
RECRUITING
Status Verified Date:
2025-09-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
Thymoma and thymic carcinoma are diseases of the thymus. Platinum-based chemotherapy is the standard treatment for these diseases. But in many cases, the disease returns after treatment. Researchers want to see if a new drug can help.
Objective:
To see if bintrafusp alfa (M7824) is an effective treatment for thymoma and thymic carcinoma.
Eligibility:
People age 18 and older who have thymoma or thymic cancer and their disease returned or progressed after treatment with at least one platinum-containing chemotherapy treatment plan.
Design:
Participants will be screened under a separate protocol. Their medical, medicine, and treatment history will be reviewed. They will have a tumor biopsy if they do not have a sample.
Participants will get the study drug once every 2 weeks as an intravenous infusion. For this, a small plastic tube is put into an arm vein.
During the study, participants will undergo the following:
Medicine review
Physical exam
Review of their symptoms and their ability to perform their normal activities
Blood and urine tests
Thigh muscle scan (using MRI)
Tumor assessment (using MRI or CT)
Heart and lung function tests
Thyroid gland test
Skin assessment.
Participants may have tumor biopsies. Some of their blood and biopsy samples will be used for gene testing.
Participants may take the study drug until their disease worsens or they cannot tolerate treatment.
Participants will have follow-up visits 2 and 6 weeks after stopping treatment. Then they will have long-term follow-up visits every 3 months. These may include imaging scans. Visits may be done by phone, with scans (if needed) done at their doctor s office.
Thymoma and thymic carcinoma are diseases of the thymus. Platinum-based chemotherapy is the standard treatment for these diseases. But in many cases, the disease returns after treatment. Researchers want to see if a new drug can help.
Objective:
To see if bintrafusp alfa (M7824) is an effective treatment for thymoma and thymic carcinoma.
Eligibility:
People age 18 and older who have thymoma or thymic cancer and their disease returned or progressed after treatment with at least one platinum-containing chemotherapy treatment plan.
Design:
Participants will be screened under a separate protocol. Their medical, medicine, and treatment history will be reviewed. They will have a tumor biopsy if they do not have a sample.
Participants will get the study drug once every 2 weeks as an intravenous infusion. For this, a small plastic tube is put into an arm vein.
During the study, participants will undergo the following:
Medicine review
Physical exam
Review of their symptoms and their ability to perform their normal activities
Blood and urine tests
Thigh muscle scan (using MRI)
Tumor assessment (using MRI or CT)
Heart and lung function tests
Thyroid gland test
Skin assessment.
Participants may have tumor biopsies. Some of their blood and biopsy samples will be used for gene testing.
Participants may take the study drug until their disease worsens or they cannot tolerate treatment.
Participants will have follow-up visits 2 and 6 weeks after stopping treatment. Then they will have long-term follow-up visits every 3 months. These may include imaging scans. Visits may be done by phone, with scans (if needed) done at their doctor s office.
Detailed Description:
Background
Platinum-based chemotherapy is the standard of care for advanced unresectable thymic epithelial tumors (TETs). However more than half of these patients experience disease recurrence and require second-line therapy.
There are no approved drugs for treatment of recurrent thymoma and thymic carcinoma and new therapeutic options are needed for patients who have disease progression on or after platinum-containing therapy.
We have demonstrated the safety and clinical activity of immune checkpoint inhibition in patients with recurrent TETs. In an ongoing trial (NCT03076554) we have shown that avelumab, an anti-programmed death ligand-1 (PD-L1) antibody, induces major responses and has an acceptable safety profile.
Combination immunotherapy is under evaluation for treatment of various cancers but has not been studied for the treatment of TETs. Immunotherapy targeting the PD-1/PD-L1 axis can be combined with other immune checkpoint inhibitors, cancer vaccines and anti-cytokine therapy.
Bintrafusp alfa, a bifunctional fusion protein that targets PD-L1 and transforming growth factor-Beta (TGF-Beta) has shown activity against heavily pre-treated solid tumors including non-small cell lung cancer previously treated with single-agent anti-PD-1/PD-L1 inhibitors.
Retrospective analysis of pre-chemotherapy tissue obtained from 20 patients with stage IV thymic carcinoma and 13 cases of stage III/IV thymoma, showed TGF-Beta expression in 65% cases of thymic carcinoma and 15% cases of thymoma with a lower median survival among patients with thymic carcinoma (30 months versus 63 months).
As part of a phase I clinical trial, treatment with bintrafusp alfa resulted in a brief period of disease stabilization and no immune-related adverse events in one patient with heavily pre-treated, WHO subtype B3 thymoma with a large disease burden
Further investigation of Bintrafusp alfa in patients with recurrent TETs is needed to define the clinical activity and safety of this drug in patients with TETs.
Primary Objectives
To determine the objective response rate (ORR) to bintrafusp alfa in participants with relapsed or refractory thymoma and thymic carcinoma.
Eligibility
Participants \>= age 18 years with histologically confirmed, unresectable thymoma or thymic carcinoma who have previously been treated with at least one platinum-containing chemotherapy regimen with progressive disease prior to study entry.
Progressive and measurable disease prior to enrollment
No history of autoimmune disease, with exception of vitiligo, autoimmune thyroid disease, or pure red cell aplasia that are adequately managed with medical therapy
Adequate renal, hepatic and hematopoietic function
Design
This will be a single-arm, phase II study to determine the clinical activity of treatment with Bintrafusp alfa in participants with relapsed or refractory thymoma and thymic carcinoma.
Bintrafusp alfa will be administered at a dose of 1200 mg intravenously once every two weeks until disease progression or development of intolerable adverse events. The two-week period will constitute one cycle.
A Simon optimal two-stage phase II trial design will be used to rule out unacceptably low response rate of 20% in favor of an improved response rate of 45%
Participants will be enrolled in 2 disease cohorts, thymoma and thymic carcinoma, with up to 17 evaluable participants of each tumor type. Accrual ceiling will be set at 44 participants to account for inevaluable participants and screen failures.
Participants who have completed 12 months of treatment with an ongoing response or disease stability (for \>= 6 months) will be given an option of discontinuing active treatment with the ability to reinstitute treatment on one occasion if radiological or clinical disease activity is noted during follow-up. All eligibility criteria should be met at the time of restarting treatment with bintrafusp alfa.
Tumor response will be assessed after completion of every third cycle (6 weeks) using modified immune-related RECIST criteria. When possible, an optional tumor biopsy will be conducted pre-treatment, after 3 doses in participants responding to treatment or at 6 weeks, whichever is sooner, to evaluate treatment-related, intra-tumoral changes.
Exploratory objectives include immune correlative studies to analyze immune cell subsets, PD-L1 expression and evaluation of soluble factors and intra-tumoral changes before and after bintrafusp alfa treatment.
Platinum-based chemotherapy is the standard of care for advanced unresectable thymic epithelial tumors (TETs). However more than half of these patients experience disease recurrence and require second-line therapy.
There are no approved drugs for treatment of recurrent thymoma and thymic carcinoma and new therapeutic options are needed for patients who have disease progression on or after platinum-containing therapy.
We have demonstrated the safety and clinical activity of immune checkpoint inhibition in patients with recurrent TETs. In an ongoing trial (NCT03076554) we have shown that avelumab, an anti-programmed death ligand-1 (PD-L1) antibody, induces major responses and has an acceptable safety profile.
Combination immunotherapy is under evaluation for treatment of various cancers but has not been studied for the treatment of TETs. Immunotherapy targeting the PD-1/PD-L1 axis can be combined with other immune checkpoint inhibitors, cancer vaccines and anti-cytokine therapy.
Bintrafusp alfa, a bifunctional fusion protein that targets PD-L1 and transforming growth factor-Beta (TGF-Beta) has shown activity against heavily pre-treated solid tumors including non-small cell lung cancer previously treated with single-agent anti-PD-1/PD-L1 inhibitors.
Retrospective analysis of pre-chemotherapy tissue obtained from 20 patients with stage IV thymic carcinoma and 13 cases of stage III/IV thymoma, showed TGF-Beta expression in 65% cases of thymic carcinoma and 15% cases of thymoma with a lower median survival among patients with thymic carcinoma (30 months versus 63 months).
As part of a phase I clinical trial, treatment with bintrafusp alfa resulted in a brief period of disease stabilization and no immune-related adverse events in one patient with heavily pre-treated, WHO subtype B3 thymoma with a large disease burden
Further investigation of Bintrafusp alfa in patients with recurrent TETs is needed to define the clinical activity and safety of this drug in patients with TETs.
Primary Objectives
To determine the objective response rate (ORR) to bintrafusp alfa in participants with relapsed or refractory thymoma and thymic carcinoma.
Eligibility
Participants \>= age 18 years with histologically confirmed, unresectable thymoma or thymic carcinoma who have previously been treated with at least one platinum-containing chemotherapy regimen with progressive disease prior to study entry.
Progressive and measurable disease prior to enrollment
No history of autoimmune disease, with exception of vitiligo, autoimmune thyroid disease, or pure red cell aplasia that are adequately managed with medical therapy
Adequate renal, hepatic and hematopoietic function
Design
This will be a single-arm, phase II study to determine the clinical activity of treatment with Bintrafusp alfa in participants with relapsed or refractory thymoma and thymic carcinoma.
Bintrafusp alfa will be administered at a dose of 1200 mg intravenously once every two weeks until disease progression or development of intolerable adverse events. The two-week period will constitute one cycle.
A Simon optimal two-stage phase II trial design will be used to rule out unacceptably low response rate of 20% in favor of an improved response rate of 45%
Participants will be enrolled in 2 disease cohorts, thymoma and thymic carcinoma, with up to 17 evaluable participants of each tumor type. Accrual ceiling will be set at 44 participants to account for inevaluable participants and screen failures.
Participants who have completed 12 months of treatment with an ongoing response or disease stability (for \>= 6 months) will be given an option of discontinuing active treatment with the ability to reinstitute treatment on one occasion if radiological or clinical disease activity is noted during follow-up. All eligibility criteria should be met at the time of restarting treatment with bintrafusp alfa.
Tumor response will be assessed after completion of every third cycle (6 weeks) using modified immune-related RECIST criteria. When possible, an optional tumor biopsy will be conducted pre-treatment, after 3 doses in participants responding to treatment or at 6 weeks, whichever is sooner, to evaluate treatment-related, intra-tumoral changes.
Exploratory objectives include immune correlative studies to analyze immune cell subsets, PD-L1 expression and evaluation of soluble factors and intra-tumoral changes before and after bintrafusp alfa treatment.
Study Oversight
Has Oversight DMC:
None
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-0097 | None | None | View |