Clinical Trials /

Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally 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®) with or without chemotherapy. 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) in Patients With Select Advanced or Metastatic Solid Tumors
  • Official Title: A Phase 1/2, Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of Combined Bempegaldesleukin (NKTR-214) and Pembrolizumab With or Without Chemotherapy 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
  • Melanoma
  • Urothelial Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
NKTR-214CD122-Biased CytokineDose Optimization, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)
PembrolizumabKeytruda®Dose Expansion, Combo of NKTR-214 + Pembrolizumab (KEYTRUDA®)
NKTR-214CD122-Biased CytokineDose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)
NKTR-214CD122-Biased CytokineDose Expansion, Combo of NKTR-214 + Pembrolizumab (KEYTRUDA®)

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®) with or without chemotherapy. 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.

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, fully humanized, engineered monoclonal antibody of IgG1 isotype
      that promotes anti-tumor effects.

      The study will evaluate the clinical benefit, safety and tolerability of combining NKTR-214
      with pembrolizumab with or without chemotherapy. Each dose expansion cohort will enroll
      approximately 100 new patients.

      Dose Optimization: will evaluate an every three-week dose regimen (q3w) of NKTR-214 in
      combination with pembrolizumab in approximately 40 patients given that the optimal dose and
      dosing schedule of NKTR-214 in combination with pembrolizumab remains unknown. The previously
      established recommended Phase 2 dose (0.006 mg/kg) of NKTR-214 was studied in combination
      with nivolumab. Tumors to be studied 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). NKTR-214 will be administered at a starting dose
      of 0.008 mg/kg q3w. Pembrolizumab will be administered at a dose of 200 mg q3w. Patients will
      undergo a fixed 3+3 dose escalation followed by intra-patient step-up dose escalation at a
      dose determined by the safety review committee after reviewing the data in the fixed 3+3 dose
      escalation.

      Dose Expansion: NKTR-214 in combination with pembrolizumab in approximately 58 patients will
      be evaluated in first-line non-small cell lung cancer (NSCLC). The NKTR-214 dose to be
      studied is 0.006 mg/kg q3w. This dose is based on the recommended phase 2 dose noted in the
      monotherapy trial with NKTR-214 (Study 15-214-01, NCT02869295) and an ongoing combination
      trial (16-214-02, NCT02983045). Pembrolizumab will be administered at a dose of 200mg q3w.
      Following data review for safety and efficacy, additional patients may be dosed using the
      findings from the dose optimization cohorts.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Optimization, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)ExperimentalCohort 1: NKTR-214 will be combined with pembrolizumab
  • NKTR-214
  • Pembrolizumab
Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)ExperimentalCohort 2: NKTR-214 will be combined with pembrolizumab
  • Pembrolizumab
  • NKTR-214
Dose Expansion, Combo of NKTR-214 + Pembrolizumab (KEYTRUDA®)ExperimentalCohort 3: NKTR-214 will be combined with pembrolizumab
  • Pembrolizumab
  • NKTR-214

Eligibility Criteria

        Inclusion Criteria:

        Dose Optimization and Dose Expansion Inclusion Criteria:

          -  Willing and able to provide written informed consent.

          -  Male or female patients, age 18 years or older at the time of signing the informed
             consent form (ICF).

          -  Life expectancy > 12 weeks from the time of enrollment as determined by the
             Investigator.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          -  Oxygen saturation ≥ 92% on room air for all indications.

          -  Measurable disease per RECIST 1.1.

          -  Patients with brain metastases are eligible if certain criteria are met.

          -  Availability of fresh or archival tumor tissue

          -  Patients must have a minimum of 6 months of response to any nonpalliative
             cancer-directed treatment

        Dose Optimization Inclusion Criteria (Multiple Solid Tumors):

          -  Melanoma:

               -  Histologically confirmed stage IV (metastatic) melanoma.

          -  Non-small Cell Lung Cancer:

               -  Histologically confirmed diagnosis of stage IV NSCLC

               -  Must not have received systemic anti-PD-L1 therapy for metastatic disease.

               -  Patients with actionable mutations with approved targeted therapy in NSCLC are
                  excluded. Testing for mutations should be performed in accordance with standard
                  of care.

          -  Urothelial Carcinoma:

               -  Histologically confirmed diagnosis of metastatic urothelial carcinoma

          -  Head and Neck Squamous Cell Carcinoma (HNSCC)

               -  Histologically confirmed diagnosis of metastatic HNSCC

          -  Hepatocellular Carcinoma (HCC)

               -  Histologically confirmed diagnosis of metastatic HCC

        Dose Expansion Inclusion Criteria (Non-Small Cell Lung Cancer):

          -  Histologically confirmed diagnosis of stage IV NSCLC.

          -  Patients must have a minimum of 6 months of response to any nonpalliative
             cancer-directed treatment.

          -  Patients with actionable mutations with approved targeted therapy in NSCLC are
             excluded. Testing for mutations should be performed per standard of care.

          -  Must not have received anti-cancer therapy for treatment of metastatic lung cancer

          -  Must not have received prior immunotherapy

        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 an active autoimmune disease

          -  History of allergy or hypersensitivity to study drug components

          -  Evidence of clinically significant interstitial lung disease or active, noninfectious
             pneumonitis.

          -  Prior surgery or radiotherapy within 14 days of therapy.

          -  For Dose Optimization Cohort 1 only: Chemotherapy or biological therapy within 28 days
             of enrollment. Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of
             enrollment. Patients with ongoing AEs related to prior cancer therapies will be
             excluded.

          -  Participant's inability to adhere to or tolerate protocol or study procedures

        NOTE: Other protocol defined Inclusion/Exclusion 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®)
Time Frame:100 days after last dose
Safety Issue:
Description:Safety and Tolerability of NKTR-214 in combination with pembrolizumab (Keytruda®) as evaluated by incidence of drug-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to drug discontinuation, and fatal AEs.

Secondary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 plus pembrolizumab (Keytruda®) with or without systemic chemotherapy in untreated metastatic NSCLC.
Time Frame:100 days after last dose
Safety Issue:
Description:Safety and Tolerability of NKTR-214 plus pembrolizumab (Keytruda®) with or without systemic chemotherapy as evaluated by incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation, deaths, and overall tolerability.
Measure:Objective response rate (ORR) per RECIST 1.1 in Dose Optimization
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR
Measure:Duration of response (DOR)
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.
Measure:Clinical benefit rate (CBR)
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:Time to Response (TTR)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:TTR will be defined for patients who had confirmed CR or confirmed PR as the time from the date of first dose to date of first documented CR or PR per RECIST 1.1.
Measure:Progression-Free Survival (PFS)
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)
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:To assess the association between efficacy measures and PD L1 expression in tumors.
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:Efficacy measures are defined as ORR and changes in PD-L1 expression from on treatment biopsy in Dose Optimization.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nektar Therapeutics

Trial Keywords

  • NKTR-214
  • Metastatic Urothelial Bladder Cancer
  • Metastatic Non-Small Cell Lung Cancer
  • Pembrolizumab
  • Keytruda®
  • Melanoma
  • Bladder
  • NSCLC
  • HCC
  • HNSCC
  • Bempegaldesleukin

Last Updated

February 1, 2021