Bladder cancer urothelial cancer
Conditions
Interventions
Bintrafusp alfa will be administered intravenously (IV) at a dose of 1200 mg
once every 2 weeks (Q2W) until confirmed disease progression, death,
unacceptable toxicity, study withdrawal, or up to 24
Sponsors
GlaxoSmithKline Research & Development Ltd.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Can give signed informed consent/assent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol 2. Eighteen (18) years at the time of signing the informed consent. 3. Histologically confirmed locally advanced or metastatic or locally advanced/unresectable urothelial carcinoma (including renal, pelvis, uterus, urinary bladder, urethra). Mixed histologies are acceptable provided transitional cell carcinoma is the predominant histology. a) Measurable disease per RECIST v1.1 criteria. b) Experienced disease progression or recurrence either (1) following platinum containing chemotherapy for metastatic or locally advanced/unresectable urothelial cancer or (2) within 12 months from completion of neo-adjuvant or adjuvant platinum-containing chemotherapy for localized muscle-invasive urothelial cancer. 4. Able to provide, a tumor tissue sample collected during screening and prior to administration of bintrafusp alfa (see SRM for details). 5. Able to provide an archival tumor sample (preferably from the most recent biopsy). Archival material is formalin fixed tumor tissue sample from a biopsy of a tumor lesion. 6. All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0) must be * Grade 1 at the time of enrollment, except alopecia, grade 2 neuropathy, or asymptomatic toxicities that are clinically stable with medical management (e.g. electrolyte abnormalities, etc.). ECOG PS 0 or 1. 7. Adequate organ system functions as defined by the laboratory assessments 8. Life expectancy of at least 12 weeks. 9. A female is eligible if she is not pregnant or breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP). OR * If a WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of <1% per year), preferably with low user dependency, as described in the following time periods: o Before the first dose of the study intervention(s), if using hormonal contraception: * -Has completed at least one 4-week cycle of an oral contraception pill and either had or has begun her menses. OR -Has used a depot contraceptive or extended-cycle oral contraceptive for least 28 days and has a documented negative pregnancy test using a highly sensitive assay. o During the intervention period o After the study intervention period (i.e., after the last dose of study intervention is administered) for at least 2 months. The Investigator evaluates the effectiveness of the contraceptive method in relationship to the first dose of study intervention. Has a negative serum or highly sensitive urine pregnancy test, as required by local regulations, within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. Male participants: * Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Male participants are eligible to participate if they agree to the following from the time of first dose of study until 125 days after the last dose of study treatment to allow for clearance
Exclusion criteria
Exclusion criteria: 1. Active brain and/or leptomeningeal disease that is symptomatic or requires therapeutic intervention. Participants with asymptomatic CNS metastases who are clinically stable as demonstrated by serial brain images and have no requirement for corticosteroids for at least 14 days prior to enrollment are eligible. 2. History of malignancy other than urothelial cancer within the last 3 years except for localized tumors that have been treated with curative intent or have not required therapy in the past 2 years. (e.g., resected non-melanoma skin cancer, etc.). 3. No more than 2 lines of systemic therapy for the treatment of meatastastic disease. If the most recent therapy was not a platinumbased regimen, the participant must have progressed on or after that therapy. 4. Cirrhosis or current unstable liver or bilary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria. 5. Current pneumonitis or history of non-infectious pneumonitis that required systemic immunosuppressive treatment. 6. Active autoimmune disease that required systemic immunosuppressive treatment within the past 2 years. 7. Received prior allogeneic/autologous bone marrow or solid organ transplant. 8. Receiving systemic corticosteroids (10 mg daily oral prednisone or equivalent) or other immunosuppressive agent within 7 days prior to study treatment. Inhaled or topical steroids are permitted. Note: a) Physiologic doses of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic absorption, including (e.g., topical, inhaled, intra-articular, ophthalmic, intranasal); corticosteroids may be continued if the participant is on a stable dose b) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are permitted. 9. Known severe hypersensitivity reactions to monoclonal antibodies or any ingredient used in the study treatment formulation (Grade 3 NCICTCAE v5). 10. Active infection requiring systemic therapy. 11. Received any live vaccine within 30 days prior first dose of intervention. 12. Known history of positive test for human immunodeficiency virus (HIV) with the exception of participants with CD4+ T-cell (CD4+) counts greater than or equal to 350 cells/uL and no history of AIDS-defining opportunistic infections. 13. Active hepatitis B virus (HBV) (HBV surface antigen-positive). 14. Active hepatitis C virus (HCV) infection, or positive HCV antibody, with the exception of participants that (1) have HCV viral load below the limits of quantitation and (2) completed curative antiviral therapy or are receiving and compliant with antiviral therapy 15. History or evidence of cardiac abnormalities within the 6 months prior to first dose of intervention which include: a. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third-degree atrioventricular block or QTc interval > 450 msec (or QTc > 480 msec for participants with bundle branch block). b. Cardiomyopathy, myocardial in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Confirmed Overall Response per RECIST 1.1 assessed by investigator. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Duration of response (DOR), progression free survival (PFS), according to RECIST 1.1, assessed by the investigator. - Confirmed Overall Response, DOR, PFS, per RECIST 1.1 as assessed by the IRC (independent review committee). - Overall survival. - Frequency and severity of AEs using NCI-CTCAE v5. - Observed bintrafusp alfa serum concentrations at the end (Ceoi) and right before infusions (Ctrough). - Number and percentage of participants that develop anti-drug antibodies against bintrafusp alfa. | — |
Countries
Netherlands
Outcome results
None listed