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A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) and of NKTR-214 in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Select Advanced or Metastatic Solid Tumors

NCT03138889

Description:

This study is to assess the safety and tolerability, and to assess the preliminary clinical benefit of NKTR-214 when combined with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®). Approximately 75 patients with stage III or stage IV melanoma, locally advanced or metastatic urothelial carcinoma, or stage IV non-small cell lung cancer (NSCLC) will be enrolled. Patients with melanoma or NSCLC cancer will receive a combination of NKTR-214 and pembrolizumab. Patients with urothelial cancer will receive a combination of NKTR-214 and atezolizumab. All drugs target the immune system and may act synergistically to promote anticancer effects.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Metastatic Urothelial Bladder Cancer or Metastatic Non-Small Cell Lung Cancer
  • Official Title: A Phase 1b, Open-label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR 214 and Anti-PD-L1 (Atezolizumab) in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer or Metastatic Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 16-214-05
  • NCT ID: NCT03138889

Conditions

  • Non-Small Cell Lung Cancer
  • Urinary Bladder Neoplasms
  • Neoplasm Metastasis

Interventions

DrugSynonymsArms
Combination of NKTR-214 + atezolizumabTecentriq (atezolizumab)Combination of NKTR-214 + Atezolizumab

Purpose

This study is to assess the safety and tolerability, determine the recommended Phase 2 dose, and assess the preliminary clinical benefit of NKTR-214 when combined with atezolizumab (Tecentriq) in select patients with urothelial bladder cancer or metastatic non-small cell lung cancer. Both drugs target the immune system and may act synergistically to promote anticancer effects.

Detailed Description

      NKTR-214 is a cytokine (investigational agent) that is designed to target CD122, a protein
      which is found on certain immune cells (known as CD8+ T Cells and Natural Killer Cells) to
      expand these cells to promote their anti-tumor effects. Atezolizumab is a fully humanized,
      engineered monoclonal antibody of IgG1 isotype against the protein programmed cell
      death-ligand 1 (PD-L1) that promotes anti-tumor effects.

      NKTR-214 will be combined with atezolizumab. The first NKTR-214 dose to be studied will be
      0.006 mg/kg based on the safety observed in the ongoing monotherapy trial with NKTR-214
      (Study 15-214-01, NCT02869295). It is estimated that approximately 36 patients will be
      enrolled to the study to different dose cohorts with doses of NKTR-214 up to 0.009 mg/kg
      administered IV every 3 weeks (q3w).
    

Trial Arms

NameTypeDescriptionInterventions
Combination of NKTR-214 + AtezolizumabExperimentalNKTR-214 in escalating doses, will be combined with atezolizumab in several cohorts.
  • Combination of NKTR-214 + atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent.

          -  Histologically confirmed locally advanced or metastatic urothelial carcinoma or
             histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC
             lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or
             anaplastic lymphoma kinase (ALK) translocation.

          -  Male or female patients, age 18 years or older at the time of signing the informed
             consent form (ICF).

          -  Life expectancy > 12 weeks as determined by the Investigator.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          -  Measurable disease per RECIST 1.1.

          -  Patients must not have received prior immunotherapy with immunomodulators, including
             but not limited to checkpoint inhibitors such as anti PD-1, anti-PD-L1, anti-PD-L2,
             anti CD137, or anti CTLA-4 (cytotoxic T lymphocyte-associated protein 4) antibody, or
             any other antibody or drug specifically targeting T cell co stimulation or checkpoint
             pathways, indoleamine 2,3 dioxydenase pathway inhibitors, cancer vaccines, adoptive
             cell therapies, or other cytokine therapies.

          -  Patients must have received no more than 1 line of platinum-containing chemotherapy
             and have disease progression during or following this therapy, or patient refuses
             standard of care.

          -  Additional criteria may apply

        Exclusion Criteria:

          -  Use of an investigational agent or an investigational device within 28 days before
             administration of first dose of study drug(s).

          -  Females who are pregnant or breastfeeding.

          -  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 with Medical Monitor approval).

          -  History of allergy or hypersensitivity to study drug components.

          -  Active malignancy not related to the current diagnosed malignancy.

          -  History of organ transplant that requires use of immune suppressive agents.

          -  Use of warfarin within 14 days of initiating study drug(s). (Note: Low molecular
             weight heparin is allowed on the study.)

          -  Evidence of clinically significant interstitial lung disease or active, noninfectious
             pneumonitis.

          -  Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients
             must have recovered from all radiation-related toxicities, not required
             corticosteroids and have not had radiation pneumonitis.

          -  Additional criteria may apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and Tolerability of NKTR-214 in combination with atezolizumab (Tecentriq)
Time Frame:100 days after last dose
Safety Issue:
Description:Safety and Tolerability of NKTR-214 in combination with atezolizumab (Tecentriq) as evaluated by incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation, deaths, and clinical laboratory test abnormalities

Secondary Outcome Measures

Measure:Efficacy of NKTR-214 in combination with atezolizumab (Tecentriq)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:Efficacy, or the preliminary anti-tumor activity, of NKTR-214 in combination with atezolizumab (Tecentriq), as assessed by the Objective Response Rate (ORR) based on RECIST 1.1
Measure:Progression-Free Survival (PFS)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause
Measure:Overall Survival (OS)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:Overall survival is defined as the time from date of first dose to the date of death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Nektar Therapeutics

Trial Keywords

  • NKTR-214
  • Atezolizumab
  • Tecentriq
  • Metastatic Urothelial Bladder Cancer
  • Metastatic Non-Small Cell Lung Cancer

Last Updated

May 1, 2017