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

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

Tracking Information

• First Submitted Date: August 3, 2016
• First Posted Date: August 16, 2016
• Last Update Posted Date: November 1, 2018
• Actual Study Start Date: December 2015
• Actual Primary Completion Date: October 31, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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 (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: A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unspecified Adult Solid Tumor, Protocol Specific

Intervention

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

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

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: August 11, 2016): 40
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 31, 2018
• Actual Primary Completion Date: October 31, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02869295
• Other Study ID Numbers: 15-214-01; 2016-001134-10 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Nektar Therapeutics
• Study Sponsor: Nektar Therapeutics
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Nektar Therapeutics
• Verification Date: October 2018