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A Randomized Study of NKTR-214 Plus Nivolumab and of Reference Chemotherapy in Cisplatin Ineligible Patients Who Have Locally Advanced or Metastatic Urothelial Cancer With Low PD-L1 Expression

NCT03785925

Description:

The main purpose of this study is to evaluate the anti-tumor activity of NKTR-214 in combination with nivolumab by assessing the objective response rate (ORR) in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients with low PD-L1 expression. The efficacy will be assessed within the experimental Arm A, while Arm B will serve as a reference arm.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Randomized Study of NKTR-214 Plus Nivolumab and of Reference Chemotherapy in Cisplatin Ineligible Patients Who Have Locally Advanced or Metastatic Urothelial Cancer With Low PD-L1 Expression
  • Official Title: A Phase 2, Randomized, Non-Comparative, Open-Label Study of NKTR-214 in Combination With Nivolumab and of Chemotherapy in Cisplatin Ineligible, Locally Advanced or Metastatic Urothelial Cancer Patients With Low PD-L1 Expression

Clinical Trial IDs

  • ORG STUDY ID: 18-214-10
  • SECONDARY ID: CA045-012
  • NCT ID: NCT03785925

Conditions

  • Urinary Bladder Neoplasm
  • Neoplasm Metastasis

Interventions

DrugSynonymsArms
NKTR-214CD122-Biased Agonist, BMS-986321Combination of NKTR-214 + nivolumab
NivolumabOpdivo®, BMS-936658Combination of NKTR-214 + nivolumab
Reference GemcitabineGemzar®Combination of gemcitabine + carboplatin
Reference CarboplatinParaplatin®Combination of gemcitabine + carboplatin

Purpose

The main purpose of this study is to evaluate the anti-tumor activity of NKTR-214 in combination with nivolumab by assessing the objective response rate (ORR) in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients with low PD-L1 expression. The efficacy will be assessed within the experimental Arm A, while Arm B will serve as a reference arm.

Trial Arms

NameTypeDescriptionInterventions
Combination of NKTR-214 + nivolumabExperimentalParticipants in Arm A will receive NKTR-214 in combination with nivolumab.
  • NKTR-214
  • Nivolumab
Combination of gemcitabine + carboplatinOtherParticipants in the reference Arm B will receive a combination of gemcitabine and carboplatin.
  • Reference Gemcitabine
  • Reference Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Provide written, informed consent to participate in the study and follow the study
             procedures

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

          -  Measurable disease per RECIST 1.1 criteria

          -  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

          -  Histologically or cytologically documented inoperable, locally advanced or metastatic
             urothelial cell carcinoma (also termed TCC)

          -  Fresh biopsy or archival tissue

          -  No prior systemic chemotherapy or investigational agent for inoperable locally
             advanced or mUC

          -  Ineligible for cisplatin

        Exclusion Criteria:

          -  Patients who have an active, known or suspected autoimmune disease

          -  Patients must not have received prior IL-2 therapy

          -  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, or any other
             antibody or drug specifically targeting T cell co-stimulation or immune checkpoint
             pathways

          -  Patients with hypertension must be on a stable antihypertensive regimen for the 14
             days prior to randomization

        Other protocol-defined inclusion/exclusion criteria could apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Blinded Independent Central Review (BICR) in patients with low programmed cell death ligand (PD-L1) expression
Time Frame:Approximately 18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of Response (DOR) by RECIST 1.1 per BICR
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Incidence of treatment-related Adverse Events (AEs)
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Nektar Therapeutics

Trial Keywords

  • Bladder
  • Bladder Cancer
  • CD122
  • Cisplatin Ineligible
  • Immuno-oncology
  • Immunotherapy
  • Locally Advanced Urothelial Cancer
  • Metastatic Urothelial Cancer
  • mUC
  • Natural Killer Cells
  • Nivolumab
  • NKTR-214
  • Opdivo®
  • PD-L1
  • Urothelial Cancer
  • Urothelial
  • Carboplatin
  • Gemcitabine
  • Paraplatin®
  • Gemzar®
  • GemCarbo

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