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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 (PROPEL)

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ClinicalTrials.gov Identifier: NCT03138889
Recruitment Status : Recruiting
First Posted : May 3, 2017
Last Update Posted : September 28, 2018
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

Brief Summary:
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.

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

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 75 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 46 patients in approved treatment settings of pembrolizumab, including patients with melanoma or non-small cell lung cancer. The second arm will evaluate a q3w dose regimen of NKTR-214 in combination with atezolizumab in up to 29 patients in approved treatment settings of atezolizumab, including patients with urothelial carcinoma. The NKTR-214 dose to be studied is 0.006 mg/kg q3w based on the safety observed in the monotherapy trial with NKTR-214 (Study 15-214-01, NCT02869295) and an ongoing combination trial (16-214-02, NCT02983045). The dose of pembrolizumab or atezolizumab to be studied will be that in their approved labelling.

For NKTR-214 + Pembrolizumab, eligible patients include:

  • Melanoma: 1st line; PD-L1 Status- all
  • NSCLC: 1st line; PD-L1 Status ≥ 50%

For NKTR-214 + Atezolizumab, eligible patients include:

  • 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
  • Disease progression during or following platinum-containing chemotherapy.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
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) or Anti-PD-L1 (Atezolizumab) in Patients With Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date : June 9, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : May 2020


Arm Intervention/treatment
Experimental: Combination of NKTR-214 + Pembrolizumab (Keytruda®)
NKTR-214 will be combined with pembrolizumab
Drug: NKTR-214
NKTR-214: The 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 will be combined with atezolizumab
Drug: NKTR-214
NKTR-214: The 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®




Primary Outcome Measures :
  1. 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

  2. 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 :
  1. 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

  2. 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

  3. 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.

  4. Clinical benefit rate (CBR) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®) [ Time Frame: Through study completion, an expected average of 2 years ]
    CBR is defined as the number of patients with confirmed complete response, confirmed partial response, or stable disease (≥ 7 weeks).

  5. Duration of response (DOR) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®) [ Time Frame: Through study completion, an expected average of 2 years ]
    DOR for patients who have confirmed complete response (CR) or confirmed partial response (PR) as the date from first documented CR or PR to the date of the first objectively documented disease progression per RECIST 1.1 or death due to any cause, whichever is earlier.



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, Older Adult)
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), metastatic NSCLC (pembrolizumab only) locally advanced or metastatic urothelial carcinoma (atezolimumab only).
  • 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 immuno-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.
  • Additional criteria may apply.

MELANOMA (pembrolizumab only)

  • Histologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system
  • Uveal 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

First-line NSCLC (pembrolizumab only)

  • Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC
  • 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.

First- or Second-line UROTHELIAL CARCINOMA (atezolizumab only)

  • Histologically or cytologically documented locally advanced or metastatic urothelial carcinoma
  • First-line patients who have disease progression within 12 months of neoadjuvant or adjuvant treatment with chemotherapy.
  • Second-line patients who have disease progression during or following platinum-containing chemotherapy.

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 active or stable brain metastases or who have a history of brain metastases.

  • 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. Prior malignancy treated with anticancer therapy (including systemic chemotherapy, radiation and/or surgery) within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.• History of organ transplant that requires use of immune suppressive agents.
  • Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
  • Prior surgery or radiotherapy within 14 days of initiating therapy. Patients must have recovered from all radiation-related toxicities, and not required corticosteroids.
  • Additional criteria may apply

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, Colorado
Investigator Site - Denver Recruiting
Aurora, Colorado, United States, 80045
United States, Louisiana
Investigator Site - New Orleans Recruiting
New Orleans, Louisiana, United States, 70816
United States, Minnesota
Investigator Site -Minneapolis Recruiting
Minneapolis, Minnesota, United States, 55426
United States, Montana
Investigator Site - Billings Recruiting
Billings, Montana, United States, 59101
United States, Nebraska
Investigator Site - Omaha Recruiting
Omaha, Nebraska, United States, 68198
United States, Nevada
Investigator Site - Las Vegas Recruiting
Las Vegas, Nevada, United States, 89169
United States, New Jersey
Investigator Site - New Brunswick Recruiting
New Brunswick, New Jersey, United States, 08901
United States, New York
Investigator Site - New York Recruiting
New York, New York, United States, 10003
United States, Tennessee
Investigator Site - Germantown Recruiting
Memphis, Tennessee, United States, 38138
United States, Washington
Investigator Site - Tacoma Recruiting
Tacoma, Washington, United States, 98405
United States, Wisconsin
Investigator Site - Milwaukee Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Nektar Therapeutics
Investigators
Study Director: Margit Tagliaferri, MD Nektar Therapeutics

Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT03138889     History of Changes
Other Study ID Numbers: 16-214-05
First Posted: May 3, 2017    Key Record Dates
Last Update Posted: September 28, 2018
Last Verified: September 2018
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:
Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Neoplasm Metastasis
Urinary Bladder Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
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