A Phase 2, single-arm study of bempegaldesleukin (NKTR-214) in combination with nivolumab in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients
- Conditions
- urotheel kankerbladder cancer10004994
- Registration Number
- NL-OMON49675
- Lead Sponsor
- PPD
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
• 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 <=
2. • Patients must have measurable disease per RECIST 1.1 criteria. • No prior
systemic chemotherapy or investigational agent for inoperable locally advanced
or mUC. • Patients must be able and willing to comply with the study visit
schedule and study procedures.
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 <= 3+4, or prostate-specific antigen (PSA) below upper limit of
normal by local laboratory and not requiring active treatment.
4. Patients who have an active, known or suspected autoimmune disease.
Patients requiring systemic treatment within the past 3 months or a documented
history of clinically severe autoimmune disease that requires systemic steroids
or immunosuppressive agents.
5. Patients with a condition requiring systemic treatment with either
corticosteroids (> 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective is:<br /><br>• To evaluate the anti-tumor activity of bempegaldesleukin (NKTR-214) in<br /><br>combination with nivolumab by assessing the objective response rate (ORR) by<br /><br>Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per<br /><br>blinded independent central review (BICR) in patients whose tumors have low<br /><br>programmed cell death ligand 1 (PD-L1) expression</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives are:<br /><br>• To evaluate the effect of NKTR-214 in combination with nivolumab by assessing<br /><br>the ORR by by RECIST 1.1 per BICR in all treated patients<br /><br>• To evaluate the effect of NKTR-214 in combination with nivolumab by assessing<br /><br>the DOR by by RECIST 1.1 per BICR in all treated patients and patients whose<br /><br>tumors have low PD-L1 expression<br /><br>• To evaluate the effect of NKTR-214 in combination with nivolumab by assessing<br /><br>the ORR and DOR by RECIST 1.1 per Investigator assessment in all treated<br /><br>patients and patients whose tumor have low PD-L1 expression.<br /><br>• To evaluate the safety and tolerability of NKTR-214 in combination with<br /><br>nivolumab </p><br>