urotheel kanker bladder cancer
Conditions
Interventions
This is a Phase 2, single arm study evaluating the safety and efficacy of NKTR
214 and nivolumab in cisplatin ineligible patients with locally advanced or
metastatic urothelial cancer.
The study ha
Sponsors
PPD
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Each patient will be entered into this study only if he/she meets all of the following criteria: • Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF). • Histologically or cytologically documented urothelial cell carcinoma (also termed TCC) including renal pelvis, ureters, urinary bladder, and urethra that is inoperable, locally advanced (T4b, any N; or any T, N2-3) or metastatic (M1, Stage IV). •Histologically or cytologically confirmed locally advanced and unresectable or metastatic urothelial cancer, including mixed urothelial cell and non-urothelial cell histologies. If the histology is mixed with non-urothelial carcinoma (e.g., squamous cell carcinoma), the urothelial cell component must be dominant (> 50% of the total histology) • Tumor tissue is required to be analyzed by the central laboratory to document PD-L1 status. • Tissue can be provided in one of two ways: -A new biopsy taken during screening -Archival tissue from either a FFPE tissue block or unstained tumor tissue sections (see Section 7.5). • Archival tissue must be obtained within 12 months prior to enrollment and with no intervening treatment. • An Eastern Cooperative Oncology Group (ECOG) performance status
Exclusion criteria
Exclusion criteria: A patient will be excluded from this study if he/she meets any of the following criteria: 1. Female patients who are pregnant or lactating, who plan to get pregnant, or who have a positive serum or urine pregnancy test. 2. Active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible if these have been treated and there is no radiographic evidence of progression for at least 4 weeks after treatment is complete (confirmed by the head imaging obtained within 28 days prior to Cycle 1 Day 1). There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to Cycle 1 Day 1. Stable dose of anticonvulsants is allowed. Treatment for CNS metastases may include whole brain radiation, stereotactic radiosurgery or neurosurgical resection. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 28 days prior to Cycle 1 Day 1 are not eligible. 3. Prior active malignancy within the previous 3 years except for locally curable cancers with negligible risk of metastases or death that have been treated with expected curative outcome, such as basal or squamous cell skin cancer, carcinoma in situ of the prostate, cervix, or breast. An incidental finding of prostate cancer (identified upon resection of the prostate) is acceptable, provided that one of the following criteria is met: T2N0M0, or Gleason score 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of Cycle 1 Day 1. 6. Patients must not have received prior IL-2 therapy. 7. Patients who have received any live / attenuated vaccine within 30 days before Cycle 1 Day 1. 8. Prior treatment with an anti PD-1, anti PD-L1, anti-PD-L2, or anti CTLA-4 antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways 9. History of allergy to study drug components. 10. History of severe hypersensitivity reaction to any monoclonal antibody. 11. History of organ, hematopoetic, or tissue transplant that requires the systemic use of immunosuppressive agents. 12. Active infection requiring systemic therapy. 13. Any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating presence of virus. 14. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally. 15. Known cardiovascular history including unstable or deteriorating cardiac disease within the previous 12 months prior to screening including but not limited to the following:a) Unstable angina or myocardial infarction b. Transient ischemic attack/cerebrovascular acci
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective is: • To evaluate the anti-tumor activity of bempegaldesleukin (NKTR-214) in combination with nivolumab by assessing the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per blinded independent central review (BICR) in patients whose tumors have low programmed cell death ligand 1 (PD-L1) expression | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives are: • To evaluate the effect of NKTR-214 in combination with nivolumab by assessing the ORR by by RECIST 1.1 per BICR in all treated patients • To evaluate the effect of NKTR-214 in combination with nivolumab by assessing the DOR by by RECIST 1.1 per BICR in all treated patients and patients whose tumors have low PD-L1 expression • To evaluate the effect of NKTR-214 in combination with nivolumab by assessing the ORR and DOR by RECIST 1.1 per Investigator assessment in all treated patients and patients whose tumor have low PD-L1 expression. • To evaluate the safety and tolerability of NKTR-214 in combination with nivolumab | — |
Countries
Netherlands
Outcome results
None listed