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

Phase 1

• Conditions: ocally advanced or metastatic urothelial bladder cancer; MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003636-79-PL
• Lead Sponsor: ektar Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-21
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 205

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.
• Tumor tissue is required to be analyzed by the central laboratory to
document PD L1 status. Tissue can be provided in one of 2 ways: 1) A
new biopsy taken during screening 2) Archival tissue from either a
formalin - fixed, paraffin - embedded (FFPE) tissue block or unstained
tumor tissue sections (see Section 7.5). Archival tissue must be within
12 months prior to enrollment and with no intervening treatment. 3) A
tracking number confirming shipment of the sample to the central
laboratory supplied prior to Cycle 1 Day 1.
• 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 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 135

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 (e.g.
GammaKnife, CyberKnife, or equivalent) 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. (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,
eczema, or psoriasis.)
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.
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 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 tranasplant that requires
the systemic use of immunosuppressive agents.
12. Active infection requiring systemic therapy within 14 days prior to
Cycle 1 Day 1
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-R

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified