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Trial record 3 of 4 for:    NKTR-214

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 (PROPEL)

This study is currently recruiting participants.
Verified November 2017 by Nektar Therapeutics
Sponsor:
ClinicalTrials.gov Identifier:
NCT03138889
First Posted: May 3, 2017
Last Update Posted: November 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Nektar Therapeutics
  Purpose
This study is to assess the safety and tolerability, define the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and to assess the preliminary clinical benefit of NKTR-214 when combined with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®). Up to 30 patients will be enrolled concurrently in each combination arm. NKTR-214 in combination with pembrolizumab will be evaluated in select patients with metastatic melanoma, urothelial bladder cancer or non-small cell Lung cancer (NSCLC). NKTR-214 in combination with atezolizumab will be evaluated in select patients with urothelial bladder cancer or NSCLC. Both drugs target the immune system and may act synergistically to promote anticancer effects.

Condition Intervention Phase
Non-Small Cell Lung Cancer Urinary Bladder Neoplasms Neoplasm Metastasis Melanoma Drug: NKTR-214 Drug: Pembrolizumab Drug: Atezolizumab Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR-214 in Combination With Anti-PD-1 (Pembrolizumab) for Patients With Locally Advanced or Metastatic Melanoma, Locally Advanced or Metastatic Urothelial Bladder Cancer, or Metastatic Non-Small Cell Lung Cancer or NKTR-214 in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer or Metastatic Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Nektar Therapeutics:

Primary Outcome Measures:
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®) [ Time Frame: 100 days after last dose ]
    Safety and Tolerability of NKTR-214 in combination with pembrolizumab (Keytruda®) or 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

  • Recommended Phase 2 Dose (RP2D) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®) [ Time Frame: 100 days after last dose ]
    To define the Recommended Phase 2 Dose (RP2D), or Maximum Tolerated Dose (MTD), of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®), by evaluating the incidence of Dose Limiting Toxicities (DLTs), drug-related AEs, SAEs, adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities


Secondary Outcome Measures:
  • Efficacy of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®) [ Time Frame: Through study completion, an expected average of 2 years ]
    Efficacy, or the preliminary anti-tumor activity, of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®), as assessed by the Objective Response Rate (ORR) based on RECIST 1.1

  • Progression-Free Survival (PFS) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®) [ Time Frame: Through study completion, an expected average of 2 years ]
    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

  • Overall Survival (OS) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®) [ Time Frame: Through study completion, an expected average of 2 years ]
    OS is defined as the time from date of first dose to the date of death.


Estimated Enrollment: 60
Actual Study Start Date: June 9, 2017
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination of NKTR-214 + Pembrolizumab (Keytruda®)
NKTR-214 in escalating doses, will be combined with pembrolizumab in several cohorts.
Drug: NKTR-214
NKTR-214: The starting dose will be a 0.006 mg/kg intravenous (IV) infusion administered over 30 (± 5) minutes q3w.
Other Name: CD122-Biased Cytokine
Drug: Pembrolizumab
Pembrolizumab (anti-PD-L) will be dosed as per label.
Other Name: Keytruda®
Experimental: Combination of NKTR-214 + Atezolizumab (Tecentriq®)
NKTR-214 in escalating doses, will be combined with atezolizumab in several cohorts.
Drug: NKTR-214
NKTR-214: The starting dose will be a 0.006 mg/kg intravenous (IV) infusion administered over 30 (± 5) minutes q3w.
Other Name: CD122-Biased Cytokine
Drug: Atezolizumab
Atezolizumab (anti-PD-L1) will be dosed as per label.
Other Name: Tecentriq®

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. Pembrolizumab is a programmed death receptor -1 (PD-1) blocking antibody and 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.

The study will evaluate the clinical benefit, safety and tolerability of combining NKTR-214 with pembrolizumab or atezolizumab and will enroll approximately 60 patients into two separate arms concurrently. The first arm will evaluate an every three-week dose regimen (q3w) of NKTR-214 in combination with pembrolizumab in up to 30 patients in approved treatment settings of pembrolizumab, including patients with melanoma, non-small cell lung cancer or bladder cancer. The second arm will evaluate a q3w dose regimen of NKTR-214 in combination with atezolizumab in up to 30 patients in approved treatment settings of atezolizumab, including patients with non-small cell lung cancer or bladder cancer. The first NKTR-214 dose to be studied will be 0.006 mg/kg q3w based on the safety observed in the monotherapy trial with NKTR-214 (Study 15-214-01, NCT02869295).

For NKTR-214 + Pembrolizumab, eligible patients include:

  • Melanoma: 1st line; PD-L1 Status- all
  • NSCLC: 1st line; PD-L1 Status ≥ 50%
  • NSCLC: 2nd line; PD-L1 Status ≥ 1%
  • Urothelial carcinoma (cisplatin ineligible): 1st line; PD-L1 Status - all
  • Urothelial carcinoma: 2nd line; PD-L1 Status - all

For NKTR-214 + Atezolizumab, eligible patients include:

  • NSCLC: 2nd line; PD-L1 Status - all
  • Urothelial carcinoma: 1st line; PD-L1 Status - all

    • Disease progression within 12 months of neoadjuvant or adjuvant treatment with chemotherapy
  • Urothelial carcinoma: 2nd line; PD-L1 Status - all
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willing and able to provide written informed consent.
  • Histologically confirmed locally advanced melanoma (pembrolizumab only), locally advanced or metastatic urothelial carcinoma, or metastatic NSCLC.
  • 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 oncology regimens, including but not limited to 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-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or other cytokine therapies.
  • MELANOMA (pembrolizumab only)

    • Histologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system
    • Ocular melanoma is excluded
    • Have not received prior anti-cancer therapy for advanced or metastatic melanoma
    • Patients with unknown BRAF mutation status may enroll so long as mutation testing is planned to be performed within 30 days of Cycle 1 Day 1
  • NSCLC

    • Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC
    • First-line (pembrolizumab only), patients must have high PD-L1 expression (Tumor Proportion Score [TPS] ≥ 50%) as determined by FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
    • Second-line (pembrolizumab or atezolizumab), patients must have experienced disease recurrence or progression during or after a prior platinum-based chemotherapy given for advanced or metastatic disease. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations and must not have received chemotherapy.
  • If patient is to receive pembrolizumab in combination with NKTR 214, PD L1 expression by TPS should be ≥ 1% as determined by an FDA-approved test.
  • UROTHELIAL CARCINOMA

    • Histologically or cytologically documented locally advanced or metastatic urothelial carcinoma
    • First-line (pembrolizumab only), patients who are not eligible for cisplatin-containing chemotherapy.
    • First-line (atezolizumab only), patients who have disease progression within 12 months of neoadjuvant or adjuvant treatment with chemotherapy.
    • Second-line (pembrolizumab or atezolizumab), patients who have disease progression during or following platinum-containing chemotherapy.
  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03138889


Contacts
Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com

Locations
United States, Nebraska
Investigator Site - Omaha Recruiting
Omaha, Nebraska, United States, 68198
United States, Tennessee
Investigator Site - Germantown Recruiting
Memphis, Tennessee, United States, 38138
United States, Washington
Investigator Site - Tacoma Recruiting
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
Nektar Therapeutics
Investigators
Study Director: Michael Imperial, MD Nektar Therapeutics
  More Information

Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT03138889     History of Changes
Other Study ID Numbers: 16-214-05
First Submitted: May 1, 2017
First Posted: May 3, 2017
Last Update Posted: November 14, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nektar Therapeutics:
NKTR-214
Atezolizumab
Tecentriq®
Metastatic Urothelial Bladder Cancer
Metastatic Non-Small Cell Lung Cancer
Pembrolizumab
Keytruda®
Melanoma
Bladder
NSCLC

Additional relevant MeSH terms:
Lung Neoplasms
Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Neoplasm Metastasis
Urinary Bladder Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Pembrolizumab
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors