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
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
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:
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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