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Trial record 2 of 3 for:    NKTR-214

A Dose Escalation and Cohort Expansion Study of CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 Antibody (Nivolumab) in Patients With Select Advanced or Metastatic Solid Tumors (PIVOT-02)

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Nektar Therapeutics
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics
ClinicalTrials.gov Identifier:
NCT02983045
First received: November 23, 2016
Last updated: May 2, 2017
Last verified: May 2017
  Purpose
This study is to determine first, the recommended Phase 2 dose of NKTR-214 when administered in combination with nivolumab, and then, the clinical benefit, safety, and tolerability of combining NKTR-214 with nivolumab in select patients with melanoma, renal cell carcinoma or non-small cell lung cancer. Both drugs target the immune system and may act synergistically to promote anti-cancer effects.

Condition Intervention Phase
Carcinoma,Non-Small-Cell Lung Carcinoma, Renal Cell Melanoma Drug: Combination of NKTR-214 + nivolumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of NKTR-214 and Nivolumab in Patients With Select Locally Advanced or Metastatic Solid Tumor Malignancies.

Resource links provided by NLM:


Further study details as provided by Nektar Therapeutics:

Primary Outcome Measures:
  • Safety of NKTR-214 in combination with nivolumab as evaluated by incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation, deaths, and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
  • Tolerability of NKTR-214 in combination with nivolumab as evaluated by incidence of Dose Limiting Toxicities (DLTs), drug-related AEs, SAEs, adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 100 days after last dose ]
  • Efficacy of NKTR-214 in combination with nivolumab as assessed by the Objective Response Rate (ORR) based on RECIST 1.1 [ Time Frame: Through study completion, an expected average of 2 years ]
    ORR will be measured by the number and percentage of patients achieving a complete or partial response as best overall response and as defined by RECIST 1.1


Secondary Outcome Measures:
  • Best Overall Response (BOR) in the population of interest [ Time Frame: Through study completion, an expected average of 2 years ]
  • Duration Of Response (DOR) [ Time Frame: Through study completion, an expected average of 2 years ]
    It is defined as time between the date of first radio-graphic images that documented objective response and the date of the first radio-graphic images that documented disease progression.

  • 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

  • Clinical Benefit Rate (CBR) [ Time Frame: Through study completion, an expected average of 2 years ]
    Clinical benefit rate will be assessed as the number of subjects with a BOR of Complete Response (CR), confirmed Partial Response (PR), or Stable Disease (SD) (where the duration of SD should be ≥ 84 days) 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 2 years ]
    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 first dose to the date of death


Other Outcome Measures:
  • Efficacy of NKTR-214 in combination with nivolumab by immune-related RECIST (irRECIST) at the RP2D. [ Time Frame: Through study completion, an expected average of 2 years ]

Estimated Enrollment: 140
Study Start Date: October 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination of NKTR-214 + nivolumab

NKTR-214 in escalating doses, will be combined with one of the two proposed doses of nivolumab. The goal of this dose escalation part of the study is to find the recommended phase 2 dose.

For the second part of the study, enrollment into a dose expansion cohort will commence once the Recommended Phase 2 Dose (RP2D) is established for this combination.

Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects.

Drug: Combination of NKTR-214 + nivolumab

Phase 1: Patients with select tumor types will receive NKTR-214 doses administered either every 21 days or every 14 days, in combination with 240 mg nivolumab (Opdivo®) every 14 days or in combination with 360 mg of nivolumab every 21 days.

Phase 2: Additional patient cohorts with select tumor types will be dosed at the recommended Phase 2 dose/schedule of NKTR-214 and nivolumab (as determined by Phase 1 of the trial).

Other Name: NKTR-214 + Opdivo®

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. Nivolumab is a full human monoclonal antibody that binds to a molecule called PD-1 on immune cells and promotes anti-tumor effects.

Approximately 40 eligible patients that enroll in the dose escalation portion of the study (Phase 1) will be assigned to one of five dose regimens of NKTR-214 in combination with nivolumab (0.006 mg/kg NKTR-214 every 21 days with 240 mg nivolumab every 14 days, 0.003 mg/kg NKTR-214 every 14 days with 240 mg nivolumab every 14 days, 0.006 mg/kg NKTR-214 every 14 days with 240 mg nivolumab every 14 days, 0.006 mg/kg NKTR-214 every 21 days with 360 mg nivolumab every 21 days, 0.003 mg/kg NKTR-214 every 21 days with 360 mg nivolumab every 21 days). Based on safety, tolerability and efficacy observed in the trial, enrollment to additional dose escalation cohorts are planned. The first phase of the study will test the safety and efficacy profile of the combination and determine which dose will be studied in Phase 2 of the overall study. During Phase 2, cohorts of patients with specific cancers will be expanded and these patients will receive the recommended Phase 2 dose and schedule of NKTR-214 in combination with nivolumab.

All patients enrolled in the study will be closely monitored to determine if there is response to the treatment as well as for any side effects that may occur. The efficacy of the combination will be assessed using objective response rate (ORR). Exploratory immunological biomarkers in plasma and tumor samples will evaluate immune activation.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed diagnosis of a locally advanced or metastatic melanoma, renal cell carcinoma (RCC), or nonsmall cell lung cancer (NSCLC)
  • Melanoma - Advanced or metastatic Melanoma who are treatment naive and are known BRAF wild-type.
  • Renal Cell Carcinoma (RCC) - Advanced or metastatic RCC who have received only 1 prior anti-angiogenic therapy, or patient refuses standard of care. Must not have received prior immunotherapy with specified immunomodulators.
  • Non-Small Cell Lung Cancer (NSCLC) - Advanced or metastatic NSCLC lacking EGFR-sensitizing mutation and/or ALK translocation. Must have experienced disease recurrence or progression during or after 1 prior platinum doublet-based chemotherapy regimen or patient refuses standard of care. Must not have received prior immunotherapy with specified immunomodulators.
  • Life expectancy >12 weeks
  • Patients must not have received prior interleukin 2 (IL 2) therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
  • Measurable disease per RECIST 1.1
  • Demonstrated adequate organ function within 14 days of treatment initiation
  • Oxygen saturation ≥ 92% on room air. NSCLC patients may use supplemental oxygen
  • 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 for at least 3 months after the last dose of study drugs
  • Patients with stable brain metastases may be enrolled if certain criteria are met
  • Sample of archival tumor tissue and fresh baseline tumor biopsies are required
  • 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
  • History of organ transplant that requires use of immune suppressive agents
  • Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
  • Prior surgery or radiotherapy within 14 days of therapy
  • Participants who have had < 28 days since the last chemotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib), 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02983045

Contacts
Contact: Nektar Recruitment 855-482-8676 StudyInquiry@nektar.com

Locations
United States, Connecticut
Local Institution - New Haven Recruiting
New Haven, Connecticut, United States, 06473
United States, New York
Local Institution - Buffalo Recruiting
Buffalo, New York, United States, 14263
Local Institution - New York Recruiting
New York, New York, United States, 10016
United States, Oregon
Local Institution - Portland Recruiting
Portland, Oregon, United States, 97213
United States, Texas
Local Institution - Houston Recruiting
Houston, Texas, United States, 77030
United States, Washington
Local Institution - Seattle Recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Nektar Therapeutics
Investigators
Study Director: Michael Imperiale, MD Nektar Therapeutics
  More Information

Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT02983045     History of Changes
Other Study ID Numbers: 16-214-02
Study First Received: November 23, 2016
Last Updated: May 2, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 25, 2017