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Trial record 1 of 1 for:    NCT03138889
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A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) 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 1, 2020
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®).

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

Dose Optimization will include first-line and second-line melanoma, non-small cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC), and hepatocellular carcinoma (HCC) regardless of PD-L1 expression status. This cohort will include patients enrolled in a 3 + 3 dose escalation and intra-patient step-up dose schemas.

The dose expansion cohort will include first-line NSCLC patients regardless of PD-L1 expression status.


Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Melanoma Urothelial Carcinoma Head and Neck Squamous Cell Carcinoma Hepatocellular Carcinoma Drug: NKTR-214 Drug: Pembrolizumab Phase 1 Phase 2

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 and will enroll approximately 100 new patients.

Dose Optimization: will evaluate an every three-week dose regimen (q3w) of NKTR-214 in combination with pembrolizumab in approximately 40 patients 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. Tumors to be studied include first-line and second-line melanoma, non-small cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC), and hepatocellular carcinoma (HCC). NKTR-214 will be administered at a starting dose of 0.008 mg/kg q3w. Pembrolizumab will be administered at a dose of 200 mg q3w. Patients will undergo a fixed 3+3 dose escalation followed by intra-patient step-up dose escalation at a dose determined by the safety review committee after reviewing the data in the fixed 3+3 dose escalation.

Dose Expansion: NKTR-214 in combination with pembrolizumab in approximately 58 patients 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR-214 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date : June 9, 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: Dose Optimization, Combo of NKTR-214 +Pembrolizumab(KEYTRUDA®)
NKTR-214 will be combined with pembrolizumab
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.
Other Name: CD122-Biased Cytokine

Drug: Pembrolizumab
Pembrolizumab (anti-PD-1) will be dosed as per label.
Other Name: Keytruda®

Experimental: Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)
NKTR-214 will be combined with pembrolizumab
Drug: Pembrolizumab
Pembrolizumab (anti-PD-1) will be dosed as per label.
Other Name: Keytruda®

Drug: NKTR-214
NKTR-214: The dose will be 0.006 mg/kg intravenous (IV) infusion administered over 30 (± 5) minutes q3w. Following data review for safety and efficacy, additional patients may be dosed at a higher dose using the findings from the dose optimization cohorts.
Other Name: CD122-Biased Cytokine




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®) [ Time Frame: 100 days after last dose ]
    Safety and Tolerability of NKTR-214 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. The overall tolerability of the NKTR-214 in combination with pembrolizumab (Keytruda®) will be evaluated by a Safety Review Committee.

  2. Recommended Phase 2 Dose (RP2D) or Maximum Tolerated Dose (MTD) or optimal dosing schedule of NKTR-214 in combination with pembrolizumab (Keytruda®) [ Time Frame: 100 days after last dose ]
    To define the Recommended Phase 2 Dose (RP2D), or Maximum Tolerated Dose (MTD), or optimal dosing schedule of NKTR-214 in combination with pembrolizumab (Keytruda®), by evaluating the incidence of Dose Limiting Toxicities (DLTs) within the DLT window (21 days after first dose), drug-related AEs, SAEs, adverse events leading to discontinuation, deaths and overall tolerability.

  3. Objective response rate (ORR) per RECIST 1.1 O in untreated metatstatic NSCLC [ Time Frame: 100 days after last dose ]
    ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®) in untreated metatstatic NSCLC. [ Time Frame: 100 days after last dose ]
    Safety and Tolerability of NKTR-214 in combination with pembrolizumab (Keytruda®) as evaluated by incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation, deaths, and overall tolerability.

  2. Objective response rate (ORR) per RECIST 1.1 O in in Dose Optimization [ Time Frame: Through study completion, an expected average of 2 years ]
    ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR

  3. Duration of response (DOR) [ 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.

  4. Clinical benefit rate (CBR) [ 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. Time to Response (TTR) [ Time Frame: Through study completion, an expected average of 2 years ]
    TTR will be defined for patients who had confirmed CR or confirmed PR as the time from the date of first dose to date of first documented CR or PR per RECIST 1.1.

  6. Progression-Free Survival (PFS) [ 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

  7. Overall Survival (OS) [ 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.

  8. To assess the association between efficacy measures and PD L1 expression in tumors. [ Time Frame: Through study completion, an expected average of 2 years ]
    Efficacy measures are defined as ORR and changes in PD-L1 expression from on treatment biopsy in Dose Optimization.



Information from the National Library of Medicine

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

Inclusion Criteria:

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 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 not have progressed within 6 months of receiving radiation, surgery adjuvant, neoadjuvant, or systemic therapy for cancer treatment.

Dose Optimization Inclusion Criteria (Multiple Solid Tumors):

  • Melanoma:

    • Histologically confirmed stage III (unresectable) or stage IV (metastatic) melanoma.
  • Non-small Cell Lung Cancer:

    • Histologically confirmed stage III (unresectable) or stage IV (metastatic).
    • Must not have received systemic anti-PD-L1 therapy for metastatic disease.
    • Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression following approved targeted therapy as applicable for these aberrations.
  • Urothelial Carcinoma:

    • Histologically or cytologically documented locally advanced or metastatic urothelial carcinoma
  • Head and Neck Squamous Cell Carcinoma (HNSCC)

    • Histologically confirmed diagnosis of recurrent and unresectable or metastatic HNSCC.
  • Hepatocellular Carcinoma (HCC)

    • Any radiographic or histologic documentation of locally advanced or metastatic HCC.

Dose Expansion Inclusion Criteria (Non-Small Cell Lung Cancer):

  • Histologically or cytologically confirmed diagnosis of stage IV NSCLC.
  • Must not have progressed within 6 months of receiving radiation, surgery, adjuvant, neoadjuvant, or systemic therapy for cancer treatment.
  • Patients with epidermal growth factor receptor (EGFR), c-ros oncogene 1 (ROS1) BRAF v600e, or anaplastic lymphoma kinase (ALK) genomic tumor aberrations are excluded
  • Must not have received anti-cancer therapy for 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 known or suspected 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.
  • Chemotherapy or biological therapy within 28 days of therapy. Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of enrollment
  • Participant's inability to adhere to or tolerate protocol or study procedures
  • 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
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Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com

Locations
Show Show 48 study locations
Sponsors and Collaborators
Nektar Therapeutics
Investigators
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Study Director: Anumeha Gupta, MD Nektar Therapeutics
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Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT03138889    
Other Study ID Numbers: 16-214-05
First Posted: May 3, 2017    Key Record Dates
Last Update Posted: September 1, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Metastatic Urothelial Bladder Cancer
Metastatic Non-Small Cell Lung Cancer
Pembrolizumab
Keytruda®
Melanoma
Bladder
NSCLC
HCC
HNSCC
Bempegaldesleukin
bempeg
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Non-Small-Cell Lung
Melanoma
Carcinoma, Hepatocellular
Carcinoma, Transitional Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Lung 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, Nerve Tissue
Nevi and Melanomas
Carcinoma, Squamous Cell
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Head and Neck Neoplasms
Pembrolizumab