Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally Advanced or Metastatic Solid Tumors

NCT ID: NCT03138889

Last Updated: 2023-03-10

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

162 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-09

Study Completion Date

2022-08-24

Brief Summary

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This study is to assess the safety and tolerability, and to assess the preliminary clinical benefit of NKTR-214 when combined with pembrolizumab (KEYTRUDA®) with or without chemotherapy.

The study is comprised of two groups; dose optimization and dose expansion cohorts.

Dose Optimization included first-line and second-line advanced or metastatic solid tumors including non-small cell lung cancer (NSCLC)

The dose expansion cohort will include first-line NSCLC patients.

Detailed Description

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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, fully humanized, engineered monoclonal antibody of IgG1 isotype that promotes anti-tumor effects.

The study will evaluate the clinical benefit, safety and tolerability of combining NKTR-214 with pembrolizumab with or without chemotherapy. Each dose expansion cohort will enroll approximately 100 new patients.

Dose Optimization evaluated an every three-week dose regimen (q3w) of NKTR-214 in combination with pembrolizumab given that the optimal dose and dosing schedule of NKTR-214 in combination with pembrolizumab remains unknown. The previously established recommended Phase 2 dose (0.006 mg/kg) of NKTR-214 was studied in combination with nivolumab.

Dose Expansion: NKTR-214 in combination with pembrolizumab will be evaluated in first-line non-small cell lung cancer (NSCLC). The NKTR-214 dose to be studied is 0.006 mg/kg q3w. This dose is based on the recommended phase 2 dose noted in the monotherapy trial with NKTR-214 (Study 15-214-01, NCT02869295) and an ongoing combination trial (16-214-02, NCT02983045). Pembrolizumab will be administered at a dose of 200mg q3w. Following data review for safety and efficacy, additional patients may be dosed using the findings from the dose optimization cohorts.

Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Optimization, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)

Cohort 1: NKTR-214 will be combined with pembrolizumab

Group Type EXPERIMENTAL

NKTR-214

Intervention Type DRUG

NKTR-214: The dose will be 0.008 mg/kg intravenous (IV) infusion administered over 30 (± 5) minutes q3w. The maximum dose of NKTR-214 will be 0.012 mg/kg. This will include a fixed 3+3 dose escalation followed by intra-patient step-up dose escalation based on tolerability.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)

Cohort 2: NKTR-214 will be combined with pembrolizumab

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

NKTR-214

Intervention Type DRUG

NKTR-214: The dose will be 0.006 mg/kg intravenous (IV) infusion.

Dose Expansion, Combo of NKTR-214 + Pembrolizumab (KEYTRUDA®)

Cohort 3: NKTR-214 will be combined with pembrolizumab

Group Type EXPERIMENTAL

NKTR-214

Intervention Type DRUG

NKTR-214: The dose will be 0.010 mg/kg intravenous (IV) infusion.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

Dose Expansion, NKTR-214 + Pembrolizumab and either Cisplatin, or Carboplatin and Pemetrexed

Cohort 4: NKTR-214 will be dosed in combination with pembrolizumab and either cisplatin, or carboplatin and pemetrexed, per investigator discretion

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Cisplatin will be dosed per the pharmacy manual

Carboplatin

Intervention Type DRUG

Carboplatin will be dosed per the pharmacy manual

Pembrolizumab

Intervention Type DRUG

Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

NKTR-214

Intervention Type DRUG

NKTR-214: The dose will be 0.006 mg/kg intravenous (IV) infusion.

Pemetrexed

Intervention Type DRUG

Pemetrexed will be dosed per the pharmacy manual

Dose Expansion, NKTR-214 + Pembrolizumab and Carboplatin and either Nab-paclitaxel or Paclitaxel

Cohort 5: NKTR-214 will be dosed in combination with pembrolizumab and carboplatin and either nab-paclitaxel or paclitaxel, per investigator discretion

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Carboplatin will be dosed per the pharmacy manual

Pembrolizumab

Intervention Type DRUG

Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

NKTR-214

Intervention Type DRUG

NKTR-214: The dose will be 0.006 mg/kg intravenous (IV) infusion.

Nab paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be dosed per local practice and label

Paclitaxel

Intervention Type DRUG

Paclitaxel will be dosed per local practice and label

Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) or Atezolizumab (TECENTRIQ®)

Cohort 0 (Before Protocol Amendment 5.0): NKTR-214 will be combined with pembrolizumab or atezolizumab

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

NKTR-214

Intervention Type DRUG

NKTR-214: The dose will be 0.006 mg/kg intravenous (IV) infusion.

Atezolizumab

Intervention Type DRUG

Atezolizumab will be dosed per current label indication

Interventions

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NKTR-214

NKTR-214: The dose will be 0.010 mg/kg intravenous (IV) infusion.

Intervention Type DRUG

Cisplatin

Cisplatin will be dosed per the pharmacy manual

Intervention Type DRUG

Carboplatin

Carboplatin will be dosed per the pharmacy manual

Intervention Type DRUG

NKTR-214

NKTR-214: The dose will be 0.008 mg/kg intravenous (IV) infusion administered over 30 (± 5) minutes q3w. The maximum dose of NKTR-214 will be 0.012 mg/kg. This will include a fixed 3+3 dose escalation followed by intra-patient step-up dose escalation based on tolerability.

Intervention Type DRUG

Pembrolizumab

Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

Intervention Type DRUG

NKTR-214

NKTR-214: The dose will be 0.006 mg/kg intravenous (IV) infusion.

Intervention Type DRUG

Nab paclitaxel

Nab-paclitaxel will be dosed per local practice and label

Intervention Type DRUG

Paclitaxel

Paclitaxel will be dosed per local practice and label

Intervention Type DRUG

Pemetrexed

Pemetrexed will be dosed per the pharmacy manual

Intervention Type DRUG

Atezolizumab

Atezolizumab will be dosed per current label indication

Intervention Type DRUG

Other Intervention Names

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CD122-Biased Cytokine Keytruda® CD122-Biased Cytokine CD122-Biased Cytokine Platinol® Paraplatin® Abraxane® Taxol® Alimta® Tecentriq®

Eligibility Criteria

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Inclusion Criteria

* Willing and able to provide written informed consent.
* Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF).
* Life expectancy \> 12 weeks from the time of enrollment as determined by the Investigator.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Oxygen saturation ≥ 92% on room air for all indications.
* Measurable disease per RECIST 1.1.
* Patients with brain metastases are eligible if certain criteria are met.
* Availability of fresh or archival tumor tissue
* Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment


* Histologically confirmed diagnosis of stage IV NSCLC.
* Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment.
* Patients with actionable mutations with approved targeted therapy in NSCLC are excluded. Testing for mutations should be performed per standard of care.
* Must not have received anti-cancer therapy for treatment of metastatic lung cancer
* Must not have received prior immunotherapy

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 autoimmune disease
* History of allergy or hypersensitivity to study drug components
* Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
* Prior surgery or radiotherapy within 14 days of therapy.
* For Dose Optimization Cohort 1 only: Chemotherapy or biological therapy within 28 days of enrollment. Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of enrollment. Patients with ongoing AEs related to prior cancer therapies will be excluded.
* Participant's inability to adhere to or tolerate protocol or study procedures
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nektar Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Nektar Therapeutics

Locations

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Highlands Oncology Group, PA - North Hills

Fayetteville, Arkansas, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Augusta University - Augusta University Medical Center

Augusta, Georgia, United States

Site Status

Ochsner Medical Center

New Orleans, Louisiana, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Park Nicollet - Frauenshuh Cancer Center

Saint Louis Park, Minnesota, United States

Site Status

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Site Status

St. Vincent Frontier Cancer Center

Billings, Montana, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

Las Vegas, Nevada, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Duke Clinical Research Institute

Durham, North Carolina, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

West Cancer Center

Germantown, Tennessee, United States

Site Status

Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Inova Melanoma and Skin Cancer Center

Fairfax, Virginia, United States

Site Status

Blue Ridge Cancer Care

Roanoke, Virginia, United States

Site Status

Northwest Medical Specialties

Tacoma, Washington, United States

Site Status

Froedtert & the Medical College of Wisconsin Froedtert Hospital

Milwaukee, Wisconsin, United States

Site Status

Epworth HealthCare

Richmond, Victoria, Australia

Site Status

Centre Hospitalier de Saint-Quentin

Saint-Quentin, , France

Site Status

Vivantes Klinikum Spandau

Berlin, , Germany

Site Status

Asklepios Fachkliniken München-Gauting

Gauting, , Germany

Site Status

LungenClinic Grosshansdorf

Großhansdorf, , Germany

Site Status

Lungenklinik Hemer

Hemer, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein

Lübeck, , Germany

Site Status

Robert-Bosch-Krankenhaus

Stuttgart, , Germany

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

HM Universitario Sanchinarro

Madrid, , Spain

Site Status

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Site Status

Countries

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United States Australia France Germany Spain

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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16-214-05

Identifier Type: -

Identifier Source: org_study_id

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