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

Description

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, Non-Small Cell Lung Cancer, Urothelial Carcinoma, or Triple Negative Breast Cancer. Both drugs target the immune system and may act synergistically to promote anti-cancer effects.

Study Start Date

October, 01 2016

Estimated Completion Date

October 2018

Interventions

  • Drug: Combination of NKTR-214 + nivolumab

Study ID

Nektar Therapeutics -- 16-214-02

Status

Recruiting

Trial ID

NCT02983045

Study Type

Interventional

Trial Phase

Phase 1/Phase 2

Enrollment Quota

250

Sponsor

Nektar Therapeutics

INCLUSION CRITERIA
  • For Dose Escalation (Phase 1) and Dose Expansion (Phase 2):
  • Willing and able to provide written informed consent
  • Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) or metastatic melanoma, RCC, NSCLC, urothelial carcinoma, or TNBC
  • Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF)
  • Life expectancy > 12 weeks
  • Patients must not have received prior interleukin-2 (IL-2) therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 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. Clinically significant toxic effect(s) of the most recent prior chemotherapy must be resolved to Grade 1 or less (except alopecia and sensory neuropathy).
  • 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 6 months after the last dose of study drugs.
  • Patients with stable brain metastases may be enrolled if certain criteria are met.
  • Fresh and archival tumor tissue available
  • Additional criteria may apply. INCLUSION CRITERIA
  • For Dose Expansion (Phase 2):
  • MELANOMA:
  • Histologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system
  • Ocular melanoma will be excluded
  • Melanoma Subpopulation A 1st-line (1L):
  • Have not received prior anti-cancer therapy for advanced or metastatic melanoma
  • Known BRAF status as per regionally acceptable V600 mutational status testing
  • Melanoma Subpopulation B (immuno-oncology [I-O] therapy relapsed/refractory):
  • 2nd
  • and 3rd-line (2-3L), patients must have received only 1 prior line of therapy with a checkpoint inhibitor (anti-PD-1 or anti-PD-L1), which must be their most recent anti-cancer treatment. Patients must have documented disease progression within 24 months during or following treatment with a checkpoint inhibitor.
  • Patients may have received only 1 prior line of therapy with molecular-targeted therapy. Patients who have not received prior molecular-targeted therapy and received only 1 prior regimen of cytotoxic chemotherapy are eligible.
  • RENAL CELL CARCINOMA (RCC):
  • Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC stage IV) RCC
  • Histologically confirmed RCC with a clear-cell component.
  • RCC Subpopulation A (I-O therapy naïve):
  • 1st
  • and 2nd-line (1-2L), patients may have received only 1 prior targeted or tyrosine kinase inhibitor therapy, or patient refuses standard of care.
  • RCC Subpopulation B (I-O relapsed/refractory):
  • 2-3L, patients must have received only 1 prior line of therapy with a checkpoint inhibitor (anti-PD-1 or anti-PD-L1), which must be their most recent anti-cancer treatment. Patients must have documented disease progression within 24 months during or following treatment with a checkpoint inhibitor.
  • Patients may have received no more than 1 prior anti-angiogenic therapy or cytotoxic chemotherapy regimen.
  • NON-SMALL CELL LUNG CANCER (NSCLC):
  • Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation
  • Patients may have experienced disease recurrence or progression during or after a prior platinum-based chemotherapy-containing regimen for advanced or metastatic disease, or patient refuses standard of care.
  • Patients who received platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation therapy given for locally advanced disease and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible.
  • NSCLC Subpopulation A (I-O therapy naïve):
  • 1-2L, patients must not have received any prior immune-oncology regimens, including but not limited to checkpoint inhibitors such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co stimulation or checkpoint pathways, indoleamine 2,3 dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or other cytokine therapies.
  • NSCLC Subpopulation B (I-O relapsed/refractory):
  • 2-3L, patients must have received only 1 prior line of therapy with a checkpoint inhibitor (anti-PD-1 or anti-PD-L1) alone or in combination with chemotherapy, which must be their most recent anti-cancer treatment. Patients must have documented disease progression within 24 months during or following treatment with a checkpoint inhibitor.
  • UROTHELIAL CARCINOMA (1L, I-O therapy naïve, cisplatin ineligible)
  • Histologically or cytologically documented locally advanced or transitional cell carcinoma of the urothelium including renal pelvis, ureters, urinary bladder, urethra ineligible for cisplatin-based chemotherapy. Patients with mixed histologies are required to have a dominant transitional cell pattern.
  • No prior chemotherapy for inoperable locally advanced or metastatic urothelial carcinoma. Prior local intravesical chemotherapy is allowed if completed at least 4 weeks prior to the initiation of study treatment.
  • For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval of more than 12 months between the last treatment administration and the date of recurrence is required to be considered treatment naïve in the metastatic setting.
  • Patients must not have received any prior immune-oncology regimens, including but not limited to checkpoint inhibitors such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways, indoleamine 2,3 dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or other cytokine therapies.
  • Patients must meet at least one of the following criteria:
  • Creatinine clearance (calculated or measured) < 60 mL/min
  • Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade ? 2 audiometric hearing loss
  • CTCAE v4.03 Grade ? 2 peripheral neuropathy
  • New York Heart Association (NYHA) Class III heart failure
  • Patient refuses standard of care
  • TRIPLE-NEGATIVE BREAST CANCER (1-2L, I-O therapy naïve)
  • Less than 1% of tumor cell nuclei test positive for estrogen and progesterone receptors determined by using standard immunohistochemistry (IHC)
  • Human epidermal growth factor 2 (HER2) negative as determined by local pathologist, using IHC or in situ hybridization
  • Patients may have received only 1 prior line of therapy with chemotherapy, adjuvant setting excluded, or patient refuses standard of care.
  • Must not have received any prior immune-oncology regimens, including but not limited to checkpoint inhibitors such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways, indoleamine 2, 3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or other cytokine therapies. EXCLUSION CRITERIA
  • For Dose Escalation (Phase 1) and Dose Expansion (Phase 2):
  • 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
  • History of allergy or hypersensitivity to study drug components
  • Active malignancy not related to the current diagnosed malignancy
  • 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
  • Participant's inability to adhere to or tolerate protocol or study procedures
  • Additional criteria may apply.
  • Gender

    All

    Ages

    18 Years and older

    Accepts Healthy Volunteers

    No

    Study Locations and Contact Information (105)

    Study Location Distance Name Phone Email
    Local Institution Boston - Boston, Massachusetts 2.6 miles None None None
    Local Institution Boston - Boston, Massachusetts 2.6 miles None None None
    Local Institution Boston - Boston, Massachusetts 2.6 miles None None None
    Local Institution Boston - Boston, Massachusetts 2.6 miles None None None
    Local Institution Boston - Boston, Massachusetts 2.6 miles None None None
    Local Institution New Haven - New Haven, Connecticut 113.5 miles None None None
    Local Institution New Haven - New Haven, Connecticut 113.5 miles None None None
    Local Institution New Haven - New Haven, Connecticut 113.5 miles None None None
    Local Institution New Haven - New Haven, Connecticut 113.5 miles None None None
    Local Institution New Haven - New Haven, Connecticut 113.5 miles None None None
    Local Institution New York 1 - New York, New York 186.5 miles None None None
    Local Institution New York 1 - New York, New York 186.5 miles None None None
    Local Institution New York 1 - New York, New York 186.5 miles None None None
    Local Institution New York 1 - New York, New York 186.5 miles None None None
    Local Institution New York 1 - New York, New York 186.5 miles None None None
    Local Institution New York 2 - New York, New York 187.1 miles None None None
    Local Institution New York 2 - New York, New York 187.1 miles None None None
    Local Institution New York 2 - New York, New York 187.1 miles None None None
    Local Institution New York 2 - New York, New York 187.1 miles None None None
    Local Institution New York 2 - New York, New York 187.1 miles None None None
    Local Institution Buffalo - Buffalo, New York 397.2 miles None None None
    Local Institution Buffalo - Buffalo, New York 397.2 miles None None None
    Local Institution Buffalo - Buffalo, New York 397.2 miles None None None
    Local Institution Buffalo - Buffalo, New York 397.2 miles None None None
    Local Institution Buffalo - Buffalo, New York 397.2 miles None None None
    Local Institution Fairfax - Fairfax, Virginia 404.7 miles None None None
    Local Institution Fairfax - Fairfax, Virginia 404.7 miles None None None
    Local Institution Fairfax - Fairfax, Virginia 404.7 miles None None None
    Local Institution Fairfax - Fairfax, Virginia 404.7 miles None None None
    Local Institution Fairfax - Fairfax, Virginia 404.7 miles None None None
    Local Institution Detroit - Detroit, Michigan 612.3 miles None None None
    Local Institution Detroit - Detroit, Michigan 612.3 miles None None None
    Local Institution Detroit - Detroit, Michigan 612.3 miles None None None
    Local Institution Detroit - Detroit, Michigan 612.3 miles None None None
    Local Institution Detroit - Detroit, Michigan 612.3 miles None None None
    Local Institution Indianapolis - Indianapolis, Indiana 805.0 miles None None None
    Local Institution Indianapolis - Indianapolis, Indiana 805.0 miles None None None
    Local Institution Indianapolis - Indianapolis, Indiana 805.0 miles None None None
    Local Institution Indianapolis - Indianapolis, Indiana 805.0 miles None None None
    Local Institution Indianapolis - Indianapolis, Indiana 805.0 miles None None None
    Local Institution Maywood - Maywood, Illinois 859.6 miles None None None
    Local Institution Maywood - Maywood, Illinois 859.6 miles None None None
    Local Institution Maywood - Maywood, Illinois 859.6 miles None None None
    Local Institution Maywood - Maywood, Illinois 859.6 miles None None None
    Local Institution Maywood - Maywood, Illinois 859.6 miles None None None
    Local Institution Atlanta - Atlanta, Georgia 932.0 miles None None None
    Local Institution Atlanta - Atlanta, Georgia 932.0 miles None None None
    Local Institution Atlanta - Atlanta, Georgia 932.0 miles None None None
    Local Institution Atlanta - Atlanta, Georgia 932.0 miles None None None
    Local Institution Atlanta - Atlanta, Georgia 932.0 miles None None None
    Local Institution St Louis - Saint Louis, Missouri 1,039.5 miles None None None
    Local Institution St Louis - Saint Louis, Missouri 1,039.5 miles None None None
    Local Institution St Louis - Saint Louis, Missouri 1,039.5 miles None None None
    Local Institution St Louis - Saint Louis, Missouri 1,039.5 miles None None None
    Local Institution St Louis - Saint Louis, Missouri 1,039.5 miles None None None
    Local Institution Gainesville - Gainesville, Florida 1,081.3 miles None None None
    Local Institution Gainesville - Gainesville, Florida 1,081.3 miles None None None
    Local Institution Gainesville - Gainesville, Florida 1,081.3 miles None None None
    Local Institution Gainesville - Gainesville, Florida 1,081.3 miles None None None
    Local Institution Gainesville - Gainesville, Florida 1,081.3 miles None None None
    Local Institution Tampa - Tampa, Florida 1,178.7 miles None None None
    Local Institution Tampa - Tampa, Florida 1,178.7 miles None None None
    Local Institution Tampa - Tampa, Florida 1,178.7 miles None None None
    Local Institution Tampa - Tampa, Florida 1,178.7 miles None None None
    Local Institution Tampa - Tampa, Florida 1,178.7 miles None None None
    Local Institution Kansas City - Kansas City, Kansas 1,252.9 miles None None None
    Local Institution Kansas City - Kansas City, Kansas 1,252.9 miles None None None
    Local Institution Kansas City - Kansas City, Kansas 1,252.9 miles None None None
    Local Institution Kansas City - Kansas City, Kansas 1,252.9 miles None None None
    Local Institution Kansas City - Kansas City, Kansas 1,252.9 miles None None None
    Local Institution Houston - Houston, Texas 1,609.9 miles None None None
    Local Institution Houston - Houston, Texas 1,609.9 miles None None None
    Local Institution Houston - Houston, Texas 1,609.9 miles None None None
    Local Institution Houston - Houston, Texas 1,609.9 miles None None None
    Local Institution Houston - Houston, Texas 1,609.9 miles None None None
    Local Institution Aurora - Aurora, Colorado 1,759.8 miles None None None
    Local Institution Aurora - Aurora, Colorado 1,759.8 miles None None None
    Local Institution Aurora - Aurora, Colorado 1,759.8 miles None None None
    Local Institution Aurora - Aurora, Colorado 1,759.8 miles None None None
    Local Institution Aurora - Aurora, Colorado 1,759.8 miles None None None
    Local Institution Seattle - Seattle, Washington 2,490.2 miles None None None
    Local Institution Seattle - Seattle, Washington 2,490.2 miles None None None
    Local Institution Seattle - Seattle, Washington 2,490.2 miles None None None
    Local Institution Seattle - Seattle, Washington 2,490.2 miles None None None
    Local Institution Seattle - Seattle, Washington 2,490.2 miles None None None
    Local Institution Portland - Portland, Oregon 2,533.3 miles None None None
    Local Institution Portland - Portland, Oregon 2,533.3 miles None None None
    Local Institution Portland - Portland, Oregon 2,533.3 miles None None None
    Local Institution Portland - Portland, Oregon 2,533.3 miles None None None
    Local Institution Portland - Portland, Oregon 2,533.3 miles None None None
    Local Institution La Jolla - La Jolla, California 2,581.5 miles None None None
    Local Institution La Jolla - La Jolla, California 2,581.5 miles None None None
    Local Institution La Jolla - La Jolla, California 2,581.5 miles None None None
    Local Institution La Jolla - La Jolla, California 2,581.5 miles None None None
    Local Institution La Jolla - La Jolla, California 2,581.5 miles None None None
    Local Institution Los Angeles - Los Angeles, California 2,605.2 miles None None None
    Local Institution Los Angeles - Los Angeles, California 2,605.2 miles None None None
    Local Institution Los Angeles - Los Angeles, California 2,605.2 miles None None None
    Local Institution Los Angeles - Los Angeles, California 2,605.2 miles None None None
    Local Institution Los Angeles - Los Angeles, California 2,605.2 miles None None None
    Local Institution Palo Alto - Stanford, California 2,694.5 miles None None None
    Local Institution Palo Alto - Stanford, California 2,694.5 miles None None None
    Local Institution Palo Alto - Stanford, California 2,694.5 miles None None None
    Local Institution Palo Alto - Stanford, California 2,694.5 miles None None None
    Local Institution Palo Alto - Stanford, California 2,694.5 miles None None None

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