A phase II study investigating preoperative bintrafusp alfa in operable urothelial carcinoma of the bladder
Bladder Cancer
Eligible patients will receive 4 doses of bintrafusp alfa (1200mg flat dose) at 14 day intervals before undergoing radical surgery. Patients will attend study visits at 6, 12 and 24 weeks following their surgery. After the 24-week post-surgical visit, patients will enter a follow up phase during which they will be contacted annually for 2 years after their surgery to collect survival and disease status data. The efficacy of bintrafusp alfa will be assessed on CT/MRI scan images and tumour tissue samples collected at baseline and after treatment with bintrafusp alfa.
1. Willing and able to provide written informed consent 2. Ability to comply with the protocol 3. Age ≥ 18 years 4. Histopathologically confirmed urothelial carcinoma (T2-T4aN1M0) of the bladder where radical cystectomy with bilateral pelvic lymph node dissection is indicated. Patients with “variant histology” such as micropapillary,plasmocytoid,nested,sarcomatoid,microcystic,squamous and adeno variants of urothelial carcinoma are required to have more than 50% of tumor tissue with transitional cell pattern. 5. Residual disease after TURBT or endoscopy (surgical opinion,cystoscopy or radiological presence). 6. Fit and planned for surgery (according to local guidelines). 7. N0-1 and M0 disease CT or MRI (within 4 weeks of enrolment). Patients with N2 disease on cross sectional imaging are excluded from the study. 8. Representative formalin-fixed paraffin embedded (FFPE) tumour samples with an associated pathology report that are determined to be available and sufficient for central testing. 9. Patients who refuse neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate. 10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 11. Negative serum pregnancy test within 14 days of Day 1 Cycle 1 for female patients of childbearing potential. 12. Highly effective method of contraception throughout the study until 2 months after the last dose of bintrafusp alfa for female patients of childbearing potential and 4 months after the last dose of bintrafusp alfa for male patients. 13. Adequate haematologic and end-organ function within 4 weeks prior to the first study treatment defined by the following: 13.1. ANC ≥ 1500 cells/μL (without granulocyte colony-stimulating factor support within 14 days prior to Cycle 1,Day 1) 13.2. WBC counts > 2500/μL 13.3. Lymphocyte count ≥ 500/μL 13.4. Platelet count ≥ 100,000/μL (without transfusion within 14 days prior to Cycle 1,Day 1) 13.5. Haemoglobin ≥ 9.0 g/dL (p
1. Pregnant and lactating female patients. 2. Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis. 3. Previous intravenous chemotherapy or immune therapy for bladder cancer. 4. Patients with prior allogeneic stem cell or solid organ transplantation. 5. Prior treatment with CD137 agonists,anti-CTLA-4,anti−programmed death−1 (PD-1),or anti−PD-L1 therapeutic antibody or pathway-targeting agents. 6. Has received any prior radiotherapy to the bladder. 7. Patients must not have had oral or intravenous (IV) steroids for 14 days prior to Cycle 1 Day 1. The use of inhaled corticosteroids,physiologic replacement doses of glucocorticoids (i.e.,for adrenal insufficiency),and mineralocorticoids (e.g.,fludrocortisone) is allowed at physiologic doses ≤10 mg/day of prednisone or equivalent. 8. Received therapeutic IV antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g.,for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible). 9. Administration of a live,attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live,attenuated vaccine will be required during the study. Seasonal flu vaccines that do not contain a live virus are permitted. 10. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]−2) within 4 weeks or five half-lives of the drug,whichever is shorter,prior to enrolment. 11. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrolment. 12. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results,including significant liver disease (such as cirrhosis,uncontrolled major seizure disorder,or superior vena cava syndrome). 13. Ma