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A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors (NKTR-214)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02869295
Recruitment Status : Completed
First Posted : August 16, 2016
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

Tracking Information
First Submitted Date  ICMJE August 3, 2016
First Posted Date  ICMJE August 16, 2016
Last Update Posted Date November 1, 2018
Actual Study Start Date  ICMJE December 2015
Actual Primary Completion Date October 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2016)
  • Safety of NKTR-214 as evaluated by incidence of drug-related adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 30 days after last dose ]
  • Tolerability of NKTR-214 as evaluated by incidence of dose limiting toxicities (DLTs), drug-related adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 30 days after last dose ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
  • Objective response rate (ORR) of NKTR-214 based on investigator review of radiographic images [ Time Frame: Through study completion, an expected average of 1 year ]
  • Best overall response (BOR) in the population of interest [ Time Frame: Through study completion, an expected average of 1 year ]
  • Duration of Response (DOR) [ Time Frame: Through study completion, an expected average of 1 year ]
    It is defined as time between the date of first radiographic documented objective response and the date of the radiographic documented disease progression.
  • Progression-Free Survival (PFS) [ Time Frame: Through study completion, an expected average of 1 year ]
    PFS is defined as the time from date of enrollment to the date of the first objectively documented tumor progression or death due to any cause
  • Clinical benefit rate (CBR) [ Time Frame: Through study completion, an expected average of 1 year ]
    Clinical benefit rate will be assessed as the number of subjects with confirmed complete response (CR), partial response (PR), or stable disease (SD) (where the duration of SD should be ≥ 3 months) divided by the total number of subjects in the Response Evaluable Population
  • Median time to response (MTR) [ Time Frame: Through study completion, an expected average of 1 year ]
    The median time to response will be summarized descriptively for subjects who have a CR or PR.
  • Overall Survival (OS) [ Time Frame: Within 3 years from study start ]
    Overall survival is defined as the time from date of enrollment to the date of death.
  • Maximum observed plasma concentration (Cmax) of NKTR-214 [ Time Frame: Day 1 of Cycle 1 and 2: pre-dose and end of administration, 0.5 hr., 3 hr., 6 hr., Post dosing on Days 2, 3, 4, 5, 8, 11, and 15 for Cycle 1 and 2 ]
  • Time of maximum observed plasma concentration (Tmax) of NKTR-214 [ Time Frame: Day 1 of Cycle 1 and 2: pre-dose and end of administration, 0.5 hr., 3 hr., 6 hr., Post dosing on Days 2, 3, 4, 5, 8, 11, and 15 for Cycle 1 and 2 ]
  • Area under the plasma concentration time curve in the dosing interval AUC(TAU) of NKTR-214 [ Time Frame: Day 1 of Cycle 1 and 2: pre-dose and end of administration, 0.5 hr., 3 hr., 6 hr., Post dosing on Days 2, 3, 4, 5, 8, 11, and 15 for Cycle 1 and 2 ]
  • Half life (t½) of NKTR-214 [ Time Frame: Day 1 of Cycle 1 and 2: pre-dose and end of administration, 0.5 hr., 3 hr., 6 hr., Post dosing on Days 2, 3, 4, 5, 8, 11, and 15 for Cycle 1 and 2 ]
  • Functional and phenotypic characterization of peripheral immune cells by flow cytometry [ Time Frame: Day 1 and Day 8 of Cycle 1 and 2 ]
  • Changes in soluble cytokines and chemokines by multiplex immunoassay [ Time Frame: Day 1 and Day 8 of Cycle 1 and 2 ]
  • Functional and phenotypic characterization of tumor immune infiltrates (TIL) by flow cytometry. [ Time Frame: Pre-dose and week 3 after first dose ]
  • Functional and phenotypic characterization of tumor immune infiltrate (TIL) by next generation sequencing of T cell receptors [ Time Frame: Pre-dose and week 3 after first dose ]
  • Functional and phenotypic characterization of tumor immune infiltrate (TIL) by immunohistochemistry (IHC) [ Time Frame: Pre-dose and week 3 after first dose ]
  • Immunogenicity analysis to assess antibodies to NKTR-214 in human serum [ Time Frame: Screening and pre-dose of Day 1 of Cycle 2 and odd-numbered cycles there after (Cycle 3, 5, 7…) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2016)
  • Objective response rate (ORR) of NKTR-214 based on investigator review of radiographic images [ Time Frame: Through study completion, an expected average of 1 year ]
  • Best overall response (BOR) in the population of interest [ Time Frame: Through study completion, an expected average of 1 year ]
  • Duration of Response (DOR) [ Time Frame: Through study completion, an expected average of 1 year ]
    It is defined as time between the date of first radiographic documented objective response and the date of the radiographic documented disease progression.
  • Progression-Free Survival (PFS) [ Time Frame: Through study completion, an expected average of 1 year ]
    PFS is defined as the time from date of enrollment to the date of the first objectively documented tumor progression or death due to any cause
  • Clinical benefit rate (CBR) [ Time Frame: Through study completion, an expected average of 1 year ]
    Clinical benefit rate will be assessed as the number of subjects with confirmed complete response (CR), partial response (PR), or stable disease (SD) (where the duration of SD should be ≥ 3 months) divided by the total number of subjects in the Response Evaluable Population
  • Median time to response (MTR) [ Time Frame: Through study completion, an expected average of 1 year ]
    The median time to response will be summarized descriptively for subjects who have a CR or PR.
  • Overall Survival (OS) [ Time Frame: Within 3 years from study start ]
    Overall survival is defined as the time from date of enrollment to the date of death.
  • Maximum observed serum concentration (Cmax) of NKTR-214 [ Time Frame: Day 1 of Cycle 1 and 2: pre-dose and end of administration, 0.5 hr., 3 hr., 6 hr., Post dosing on Days 2, 3, 4, 5, 8, 11, and 15 for Cycle 1 and 2 ]
  • Time of maximum observed serum concentration (Tmax) of NKTR-214 [ Time Frame: Day 1 of Cycle 1 and 2: pre-dose and end of administration, 0.5 hr., 3 hr., 6 hr., Post dosing on Days 2, 3, 4, 5, 8, 11, and 15 for Cycle 1 and 2 ]
  • Area under the serum concentration time curve in the dosing interval AUC(TAU) of NKTR-214 [ Time Frame: Day 1 of Cycle 1 and 2: pre-dose and end of administration, 0.5 hr., 3 hr., 6 hr., Post dosing on Days 2, 3, 4, 5, 8, 11, and 15 for Cycle 1 and 2 ]
  • Half life (t½) of NKTR-214 [ Time Frame: Day 1 of Cycle 1 and 2: pre-dose and end of administration, 0.5 hr., 3 hr., 6 hr., Post dosing on Days 2, 3, 4, 5, 8, 11, and 15 for Cycle 1 and 2 ]
  • Functional and phenotypic characterization of peripheral immune cells by flow cytometry [ Time Frame: Day 1 and Day 8 of Cycle 1 and 2 ]
  • Changes in soluble cytokines and chemokines by multiplex immunoassay [ Time Frame: Day 1 and Day 8 of Cycle 1 and 2 ]
  • Functional and phenotypic characterization of tumor immune infiltrates (TIL) by flow cytometry. [ Time Frame: Pre-dose and week 3 after first dose ]
  • Functional and phenotypic characterization of tumor immune infiltrate (TIL) by next generation sequencing of T cell receptors [ Time Frame: Pre-dose and week 3 after first dose ]
  • Functional and phenotypic characterization of tumor immune infiltrate (TIL) by immunohistochemistry (IHC) [ Time Frame: Pre-dose and week 3 after first dose ]
  • Immunogenicity analysis to assess antibodies to NKTR-214 in human serum [ Time Frame: Screening and pre-dose of Day 1 of Cycle 2 and odd-numbered cycles there after (Cycle 3, 5, 7…) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors
Official Title  ICMJE An Open-Label, Multicenter, Dose Escalation And Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumor Malignancies
Brief Summary This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR-214 in adult patients with locally advanced or metastatic solid tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unspecified Adult Solid Tumor, Protocol Specific
Intervention  ICMJE Drug: NKTR-214
Participants in the dose escalation cohorts will be treated every 21 days (q21d) or every 14 days (q14d) until tumor progression.
Study Arms  ICMJE Experimental: NKTR-214 Dose Escalation
This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR--214 in adult patients with locally advanced and metastatic solid tumors. The Phase 1 stage of the study is designed as an open-label dose escalation trial of NKTR--214 in participants with locally advanced or metastatic solid tumors. The goal of the dose escalation stage of the study is to find the recommended phase 2 dose, to evaluate the efficacy of NKTR--214 by assessing the objective response rate and to evaluate the safety of NKTR-214. Immunological biomarkers in plasma and tumor samples will also be measured.
Intervention: Drug: NKTR-214
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: August 11, 2016)
40
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 31, 2018
Actual Primary Completion Date October 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor.
  • Received 1 or 2 prior lines of therapy.
  • Life expectancy >12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
  • Measurable disease per RECIST v1.1.
  • Demonstrated adequate organ function within 14 days of treatment initiation.
  • Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior system anticancer therapy, radiotherapy or surgery.
  • Women of childbearing potential must agree to use highly effective methods of birth control.
  • All participants must agree to use double barrier contraception during study participation and for at least 2 months after the last dose of study drug.
  • Additional criteria may apply.

Exclusion Criteria:

  • Use of an investigational agent or an investigational device within 28 days before administration of first dose of NKTR-214.
  • Females who are pregnant or breastfeeding.
  • Participants who have an active autoimmune disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
  • Active central nervous system (CNS) metastases.
  • Prior surgery or radiotherapy within 14 days of therapy.
  • Participants who have had < 28 days since the last chemotherapy, immunotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobretinib), or systemic or inhaled steroid therapy at doses greater than 10mg of prednisone or equivalent before administration of the first dose of study medication.
  • Participants' inability to adhere to or tolerate protocol or study procedures.
  • Additional criteria may apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02869295
Other Study ID Numbers  ICMJE 15-214-01
2016-001134-10 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nektar Therapeutics
Study Sponsor  ICMJE Nektar Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Nektar Therapeutics
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP