Clinical Trials /

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

NCT03138889

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) and of NKTR-214 in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Select Advanced or Metastatic Solid Tumors
  • Official Title: A Phase 1b, Open-label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR-214 in Combination With Anti-PD-1 (Pembrolizumab) or Anti-PD-L1 (Atezolizumab) in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 16-214-05
  • NCT ID: NCT03138889

Conditions

  • Non-Small Cell Lung Cancer
  • Urinary Bladder Neoplasms
  • Neoplasm Metastasis
  • Melanoma

Interventions

DrugSynonymsArms
NKTR-214CD122-Biased CytokineCombination of NKTR-214 + Pembrolizumab (Keytruda®)
PembrolizumabKeytruda®Combination of NKTR-214 + Pembrolizumab (Keytruda®)
AtezolizumabTecentriq®Combination of NKTR-214 + Atezolizumab (Tecentriq®)

Purpose

This study is to assess the safety and tolerability, and to assess the preliminary clinical benefit of NKTR-214 when combined with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®). Approximately 75 patients with stage III or stage IV melanoma, locally advanced or metastatic urothelial carcinoma, or stage IV non-small cell lung cancer (NSCLC) will be enrolled. Patients with melanoma or NSCLC cancer will receive a combination of NKTR-214 and pembrolizumab. Patients with urothelial cancer will receive a combination of NKTR-214 and atezolizumab. All drugs target the immune system and may act synergistically to promote anticancer effects.

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 antibody and atezolizumab is a fully humanized, engineered
      monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1
      (PD-L1) that promotes anti-tumor effects.

      The study will evaluate the clinical benefit, safety and tolerability of combining NKTR-214
      with pembrolizumab or atezolizumab and will enroll approximately 75 patients into two
      separate arms concurrently. The first arm will evaluate an every three-week dose regimen
      (q3w) of NKTR-214 in combination with pembrolizumab in up to 46 patients in approved
      treatment settings of pembrolizumab, including patients with melanoma or non-small cell lung
      cancer. The second arm will evaluate a q3w dose regimen of NKTR-214 in combination with
      atezolizumab in up to 29 patients in approved treatment settings of atezolizumab, including
      patients with urothelial carcinoma. The NKTR-214 dose to be studied is 0.006 mg/kg q3w based
      on the safety observed in the monotherapy trial with NKTR-214 (Study 15-214-01, NCT02869295)
      and an ongoing combination trial (16-214-02, NCT02983045). The dose of pembrolizumab or
      atezolizumab to be studied will be that in their approved labelling.

      For NKTR-214 + Pembrolizumab, eligible patients include:

        -  Melanoma: 1st line; PD-L1 Status- all

        -  NSCLC: 1st line; PD-L1 Status ≥ 50%

      For NKTR-214 + Atezolizumab, eligible patients include:

        -  Urothelial carcinoma: 1st line; PD-L1 Status - all

        -  Disease progression within 12 months of neoadjuvant or adjuvant treatment with
           chemotherapy

        -  Urothelial carcinoma: 2nd line; PD-L1 Status - all

        -  Disease progression during or following platinum-containing chemotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Combination of NKTR-214 + Pembrolizumab (Keytruda®)ExperimentalNKTR-214 will be combined with pembrolizumab
  • NKTR-214
  • Pembrolizumab
Combination of NKTR-214 + Atezolizumab (Tecentriq®)ExperimentalNKTR-214 will be combined with atezolizumab
  • NKTR-214
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent.

          -  Histologically confirmed locally advanced melanoma (pembrolizumab only), metastatic
             NSCLC (pembrolizumab only) locally advanced or metastatic urothelial carcinoma
             (atezolimumab only).

          -  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.

          -  Measurable disease per RECIST 1.1.

          -  Patients must not have received prior immuno-oncology regimens, including but not
             limited to inhibitors such as anti PD-1, anti-PD-L1, anti-PD-L2, anti CD137, or anti
             CTLA-4 (cytotoxic T lymphocyte-associated protein 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.

          -  Additional criteria may apply.

        MELANOMA (pembrolizumab only)

          -  Histologically confirmed stage III (unresectable) or stage IV melanoma, as per
             American Joint Committee on Cancer (AJCC) staging system

          -  Uveal melanoma is excluded

          -  Have not received prior anti-cancer therapy for advanced or metastatic melanoma

          -  Patients with unknown BRAF mutation status may enroll so long as mutation testing is
             planned to be performed within 30 days of Cycle 1 Day 1

        First-line NSCLC (pembrolizumab only)

          -  Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC

          -  Patients must have high PD-L1 expression (Tumor Proportion Score [TPS] ≥ 50%) as
             determined by FDA-approved test, with no epidermal growth factor receptor (EGFR) or
             anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

        First- or Second-line UROTHELIAL CARCINOMA (atezolizumab only)

          -  Histologically or cytologically documented locally advanced or metastatic urothelial
             carcinoma

          -  First-line patients who have disease progression within 12 months of neoadjuvant or
             adjuvant treatment with chemotherapy.

          -  Second-line patients who have disease progression during or following
             platinum-containing chemotherapy.

        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 active or stable brain metastases or who have a history of brain
             metastases.

          -  Patients who have an active, known or suspected autoimmune disease. Patients requiring
             systemic treatment within the past 3 months or a documented history of clinically
             severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
             (Exceptions include any patient on 10 mg or less of prednisone or equivalent, patients
             with vitiligo, hypothyroidism stable on hormone replacement, Type I diabetes, Graves'
             disease, Hashimoto's disease, alopecia areata, eczema, or with Medical Monitor
             approval).

          -  History of allergy or hypersensitivity to study drug components. Prior malignancy
             treated with anticancer therapy (including systemic chemotherapy, radiation and/or
             surgery) within the previous 3 years except for locally curable cancers that have been
             apparently cured, such as basal or squamous cell skin cancer, superficial bladder
             cancer, or carcinoma in situ of the prostate, cervix, or breast.• 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 initiating therapy. Patients must have
             recovered from all radiation-related toxicities, and not required corticosteroids.

          -  Additional criteria may apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®)
Time Frame:100 days after last dose
Safety Issue:
Description:Safety and Tolerability of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®) 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

Secondary Outcome Measures

Measure:Efficacy of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:Efficacy, or the preliminary anti-tumor activity, of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®), as assessed by the Objective Response Rate (ORR) based on RECIST 1.1
Measure:Progression-Free Survival (PFS) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description: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
Measure:Overall Survival (OS) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:OS is defined as the time from date of first dose to the date of death.
Measure:Clinical benefit rate (CBR) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:CBR is defined as the number of patients with confirmed complete response, confirmed partial response, or stable disease (≥ 7 weeks).
Measure:Duration of response (DOR) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nektar Therapeutics

Trial Keywords

  • NKTR-214
  • Atezolizumab
  • Tecentriq®
  • Metastatic Urothelial Bladder Cancer
  • Metastatic Non-Small Cell Lung Cancer
  • Pembrolizumab
  • Keytruda®
  • Melanoma
  • Bladder
  • NSCLC

Last Updated