A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma
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|ClinicalTrials.gov Identifier: NCT04501094|
Recruitment Status : Recruiting
First Posted : August 6, 2020
Last Update Posted : July 14, 2021
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 M7824. The drug is a new immunotherapy that blocks the pathways that cancer cells use to stop the immune system from fighting cancer.
To learn if M7824 can help the immune system s ability to fight urothelial cancer.
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
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.
|Condition or disease||Intervention/treatment||Phase|
|Urothelial Cancer||Drug: Bintrafusp alfa (M7824)||Phase 2|
- Metastatic urothelial carcinoma is lethal and incurable with a median overall survival of 14 months from diagnosis.
- Immune checkpoint inhibitors targeting the PD-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 FDA-approved for for second-line 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.
-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 CR/PR
- Cohort 2B: previously had SD/PD
- 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
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma|
|Actual Study Start Date :||October 26, 2020|
|Estimated Primary Completion Date :||May 1, 2024|
|Estimated Study Completion Date :||December 1, 2024|
Experimental: 1/Arm 1
Treatment with Bintrafusp alfa (M7824)
Drug: Bintrafusp alfa (M7824)
1200 mg administered IV every two weeks
- Objective response rate (ORR) [ Time Frame: 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 ]the fraction of evaluable patients with a PR or CR at the end of treatment with Bintrafusp alfa (M7824)
- safety of Bintrafusp alfa (M7824) [ Time Frame: until confirmed progression, unacceptable toxicity or trial withdrawal ]The fraction of patients with toxicity will be reported by grade and type of toxicity identified.
- Progression free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first ]duration of time from start of treatment to time of progression or death, whichever occurs first
- Overall Survival (OS) [ Time Frame: Time from treatment to the date of death from any cause ]Time from the start of treatment that patients are still alive.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04501094
|Contact: Lisa Ley, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Andrea B Apolo, M.D.||National Cancer Institute (NCI)|