AzTrials
AzTrials

Non-Small Cell Lung CancerPhase 1/2PROPELNCT03138889

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

A Phase 1/2 study testing NKTR-214, Pembrolizumab and Cisplatin in people with Non-Small Cell Lung Cancer, run by Nektar Therapeutics at 38 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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®) with or without chemotherapy. The study is comprised of two groups; dose optimization and dose expansion cohorts. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
NKTR-214, Pembrolizumab and Cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
162 participants
Where
38 sitesin 5 countries
Study dates
9 Jun 2017to 24 Aug 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Dose Optimization and Dose Expansion 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.
Show all 16Show fewer
  • 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
  • Dose Expansion Inclusion Criteria (Non-Small Cell Lung Cancer):
  • 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

Who cannot join

  • 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.
Show all 9Show fewer
  • 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
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Trial locations and contacts

38 sites in 5 countries.

38 sites in 5 countries

United States23 sites
  • Augusta University - Augusta University Medical Center

    Augusta, Georgia, 30912

  • University of Colorado Anschutz Medical Campus

    Aurora, Colorado, 80045

  • St. Vincent Frontier Cancer Center

    Billings, Montana, 59101

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Duke Clinical Research Institute

    Durham, North Carolina, 27705

  • Inova Melanoma and Skin Cancer Center

    Fairfax, Virginia, 22031

  • Highlands Oncology Group, PA - North Hills

    Fayetteville, Arkansas, 72703

  • West Cancer Center

    Germantown, Tennessee, 38138

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

    Las Vegas, Nevada, 89169

  • Froedtert & the Medical College of Wisconsin Froedtert Hospital

    Milwaukee, Wisconsin, 53226

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

    Nashville, Tennessee, 37203

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

  • Ochsner Medical Center

    New Orleans, Louisiana, 70816

  • New York University Langone Medical Center

    New York, New York, 10016

  • Columbia University Medical Center

    New York, New York, 10032

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Blue Ridge Cancer Care

    Roanoke, Virginia, 24153

  • Park Nicollet - Frauenshuh Cancer Center

    Saint Louis Park, Minnesota, 55426

  • California Pacific Medical Center

    San Francisco, California, 94115

  • Washington University School of Medicine in St. Louis

    St Louis, Missouri, 63156

  • Northwest Medical Specialties

    Tacoma, Washington, 98405

Other trials in United States

Spain7 sites
  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08025

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario Insular de Gran Canaria

    Las Palmas de Gran Canaria, 35016

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040

  • HM Universitario Sanchinarro

    Madrid, 28050

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026

Other trials in Spain

Germany6 sites
  • Vivantes Klinikum Spandau

    Berlin, 13585

  • Asklepios Fachkliniken München-Gauting

    Gauting, 82131

  • LungenClinic Grosshansdorf

    Großhansdorf, 22927

  • Lungenklinik Hemer

    Hemer, 58675

  • Universitätsklinikum Schleswig-Holstein

    Lübeck, 23538

  • Robert-Bosch-Krankenhaus

    Stuttgart, 70376

Other trials in Germany

Australia1 site
  • Epworth HealthCare

    Richmond, Victoria, 3121

Other trials in Australia

France1 site
  • Centre Hospitalier de Saint-Quentin

    Saint-Quentin, 2100

Other trials in France

About this study

Official title: A Phase 1/2, Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of Combined Bempegaldesleukin (NKTR-214) and Pembrolizumab With or Without Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors

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.

Read the 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, 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.

Keywords
NKTR-214, Metastatic Non-Small Cell Lung Cancer, Pembrolizumab, Keytruda®, NSCLC, Bempegaldesleukin
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NKTR-214Drug

    Also called CD122-Biased Cytokine

    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.

  • PembrolizumabDrug

    Also called Keytruda®

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

  • NKTR-214Drug

    Also called CD122-Biased Cytokine

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

  • NKTR-214Drug

    Also called CD122-Biased Cytokine

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

  • CisplatinDrug

    Also called Platinol®

    Cisplatin will be dosed per the pharmacy manual

  • CarboplatinDrug

    Also called Paraplatin®

    Carboplatin will be dosed per the pharmacy manual

  • Nab paclitaxelDrug

    Also called Abraxane®

    Nab-paclitaxel will be dosed per local practice and label

  • PaclitaxelDrug

    Also called Taxol®

    Paclitaxel will be dosed per local practice and label

  • PemetrexedDrug

    Also called Alimta®

    Pemetrexed will be dosed per the pharmacy manual

  • AtezolizumabDrug

    Also called Tecentriq®

    Atezolizumab will be dosed per current label indication

Study groups in NCT03138889
Study groupRoleWhat they receive
Dose Optimization, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)ExperimentalCohort 1: NKTR-214 will be combined with pembrolizumab
Receives: Drug: NKTR-214; Drug: Pembrolizumab
Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)ExperimentalCohort 2: NKTR-214 will be combined with pembrolizumab
Receives: Drug: Pembrolizumab; Drug: NKTR-214
Dose Expansion, Combo of NKTR-214 + Pembrolizumab (KEYTRUDA®)ExperimentalCohort 3: NKTR-214 will be combined with pembrolizumab
Receives: Drug: Pembrolizumab; Drug: NKTR-214
Dose Expansion, NKTR-214 + Pembrolizumab and either Cisplatin, or Carboplatin and PemetrexedExperimentalCohort 4: NKTR-214 will be dosed in combination with pembrolizumab and either cisplatin, or carboplatin and pemetrexed, per investigator discretion
Receives: Drug: Pembrolizumab; Drug: NKTR-214; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed
Dose Expansion, NKTR-214 + Pembrolizumab and Carboplatin and either Nab-paclitaxel or PaclitaxelExperimentalCohort 5: NKTR-214 will be dosed in combination with pembrolizumab and carboplatin and either nab-paclitaxel or paclitaxel, per investigator discretion
Receives: Drug: Pembrolizumab; Drug: NKTR-214; Drug: Carboplatin; Drug: Nab paclitaxel; Drug: Paclitaxel
Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) or Atezolizumab (TECENTRIQ®)ExperimentalCohort 0 (Before Protocol Amendment 5.0): NKTR-214 will be combined with pembrolizumab or atezolizumab
Receives: Drug: Pembrolizumab; Drug: NKTR-214; Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing Dose-Limiting Toxicities in Dose Optimization Cohort 1a

    DLTs were assesses in the Dose Optimization Cohort 1 a, which had doses of NKTR-214 as 0.008 mg/kg, 0.010 mg/kg, and 0.012 m/kg, I combination with pembrolizumab at 200 mg.

    A single DLT (hypotension) was reported in 1 patient in dose optimization Cohort 1a.

    Measured: DLTs were assessed at 21 days from Cycle 1

  2. Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] for Dose Optimization Cohort 1a.

    Safety and Tolerability of NKTR-214 (starting at dose of 0.008 mg/kg) in combination with pembrolizumab (Keytruda®) as evaluated by incidence of drug-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to drug discontinuation, and fatal AEs.

    Measured: AEs reported starting immediately after first dose of study drug(s) until 100 days after the last dose of all study drugs, up to approximately 28 months.

  3. Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by RECIST 1.1 of NKTR-214 Plus Pembrolizumab for Dose Expansion Cohorts 2 and 3.

    ORR per BICR by RECIST 1.1 for the Response Evaluable Population dose expansion Cohorts 2 and 3.

    ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.

    The Response Evaluable Population was subjects who received at least 1 dose (or partial dose) of study drug, had measurable disease (per RECIST 1.1) at baseline, and had at least 1 post-baseline assessment of tumor response.

    Measured: Until disease progression, death, unacceptable toxicity, symptomatic deterioration, Investigator's decision to discontinue treatment, patient withdrew consent or lost to follow-up, or study terminated by Sponsor; or until maximum of 2 years.

  4. Objective Response Rate (ORR) Per Investigator's Assessment by RECIST 1.1 of NKTR-214 at a Dose of 0.006 mg/kg With Pembrolizumab and Platinum-based Chemotherapy for Dose Expansion Cohorts 4+5.

    ORR per Investigator's Assessment* by RECIST 1.1 for the Response Evaluable Population dose expansion Cohorts 4 +5. The Response Evaluable Population was subjects who received at least 1 dose (or partial dose) of study drug, had measurable disease (per RECIST 1.1) at baseline, and had at least 1 post-baseline assessment of tumor response.

    Objective response is the sum of confirmed complete response and confirmed partial response.

    *Efficacy endpoint for Cohort 4 +5 is per Investigator's Assessment due to the early termination of the study and incompleteness of BICR data for these cohorts.

    Measured: Until disease progression, death, unacceptable toxicity, symptomatic deterioration, Investigator's decision to discont. treatment, patient withdrew consent or lost to follow-up, or study terminated by Sponsor; or until maximum of 2 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2017
  2. Study start9 Jun 2017
  3. Primary completion5 Jul 2022
  4. Study completion24 Aug 2022

Why it stopped: Sponsor decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
162 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03138889
Sponsor's protocol ID
16-214-05
Acronym
PROPEL
Status last verified
Mar 2023
First submitted
1 May 2017
Last updated
10 Mar 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NKTR-214, Pembrolizumab and Cisplatin in people with Non-Small Cell Lung Cancer, run by Nektar Therapeutics at 38 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Spain, Germany, Australia, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose-Limiting Toxicities in Dose Optimization Cohort 1a (time frame: DLTs were assessed at 21 days from Cycle 1). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2023.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in