A study in patients with bladder cancer using a combination of nivolumab and NKTR-214 with chemotherapy.

Phase 1

Conditions: ocally advanced or metastatic, low PD-L1 expression urothelial bladder cancer
MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-003636-79-FR

Lead Sponsor: ektar Therapeutics

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 165

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).
• Patients must have histologically or cytologically documented inoperable, locally advanced (T4b, any N; or any T, N2-3) or metastatic (M1, Stage IV) urothelial cell carcinoma (also termed transitional cell carcinoma) including renal pelvis, ureters, urinary bladder and urethra.
• Patients with mixed histologies are required to have a dominant transitional cell pattern.
• Sample of fresh baseline tumor biopsies (fresh baseline biopsy is defined as a biopsy specimen taken during screening) is required to document PD L1 status. Patients who cannot provide a fresh baseline tumor biopsy, must provide archival tissue either from a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections (minimum of 15 to 25 slides).
• Central laboratory must confirm receipt of evaluable tumor tissue prior to randomization. For those patients with no local PD-L1 testing, central laboratory testing must be completed and patient confirmed as low PD L1 prior to randomization.
• Tumor must be PD-L1 low (defined by a Combined Positive Score [CPS] of < 10 utilizing the Dako PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay). Patients with validated local testing confirming low PD L1 status by the 22C3 pharmDx assay may enroll and start treatment. They must, however, submit a fresh baseline or archival tumor biopsy for confirmation. If the central PD L1 testing returns high PD-L1 (i.e., CPS = 10), these patients will continue to be treated, but will not be included in the efficacy evaluation and will be replaced.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status = 2.
• Patients must have measurable disease per RECIST 1.1 criteria, and have adequate organ function.
• Patients must be able and willing to comply with the study visit schedule and study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

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 8 weeks after treatment is complete (confirmed by the head imaging obtained within 28 days prior to randomization). There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to randomization. Stable dose of anticonvulsants is required within 14 days prior to randomization. Treatment for CNS metastases may include stereotactic radiosurgery (e.g. GammaKnife, CyberKnife, or equivalent) or neurosurgical resection. Patients who received whole brain radiation therapy are not eligible.
3. Prior active malignancy within the previous 3 years except for locally curable cancers that have been apparently cured, 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 the following criteria are met: Stage T2N0M0 or lower; Gleason score = 6, and prostate specific antigen (PSA) below lower limit of normal by local laboratory.
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. (Exceptions include any patient on 10 mg or less of prednisone or equivalent, patients with vitiligo, hypothyroidism stable on hormone replacement, Type I diabetes, Graves’ disease, Hashimoto's disease, alopecia areata, or eczema.)
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 randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
6. Patients must not have received prior IL-2 therapy.
7. Patients who have received a live / attenuated vaccine within 30 days before first treatment.
8. Prior treatment with an anti PD-1, anti PD-L1, or anti cytotoxic T lymphocyte associated protein 4 (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 transplant that requires use of immune suppressive 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, e.g. hepatitis B surface antigen (HBsAg) positive, or hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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