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BRIEF TITLE: NKTR-214 in Combination With Anti-PD-1 (Pembrolizumab) or Anti-PD-L1 (Atezolizumab) in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase 1/2, Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR-214 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors


  • Org Study ID: 16-214-05
  • Secondary ID:
  • NCT ID: NCT03138889
  • NCT Alias:
  • Sponsor: Nektar Therapeutics - Industry
  • Source: Nektar Therapeutics

Brief Summary

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.

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 and 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.

Overal Status Start Date Phase Study Type
Recruiting June 9, 2017 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®)

Primary Outcome 1 - Time Frame: 100 days after last dose

Primary Outcome 2 - Measure: Recommended Phase 2 Dose (RP2D) or Maximum Tolerated Dose (MTD) or optimal dosing schedule of NKTR-214 in combination with pembrolizumab (Keytruda®)

Primary Outcome 2 - Time Frame: 100 days after last dose

Primary Outcome 3 - Measure: Objective response rate (ORR) per RECIST 1.1 O in untreated metatstatic NSCLC

Primary Outcome 3 - Time Frame: 100 days after last dose

Condition:

  • Non-Small Cell Lung Cancer
  • Melanoma
  • Urothelial Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma

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 as determined by the Investigator.

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

- Oxygen saturation ≥ 92% on room air for all indications; oxygen saturation ≥ 90% on
room air for lung cancer considered to be due to lung metastasis.

- Measurable disease per RECIST 1.1.

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

- Availability of fresh or archival tumor tissue.

Dose Optimization Inclusion Criteria (Multiple Solid Tumors):

- Melanoma:

- Histologically confirmed stage III (unresectable) or stage IV (metastatic)
melanoma.

- Non-small Cell Lung Cancer:

- Histologically confirmed stage III (unresectable) or stage IV (metastatic).

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

- Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma
kinase (ALK) genomic tumor aberrations should have disease progression following
approved targeted therapy as applicable for these aberrations.

- Urothelial Carcinoma:

- Histologically or cytologically documented locally advanced or metastatic
urothelial carcinoma

- Head and Neck Squamous Cell Carcinoma (HNSCC)

- Histologically confirmed diagnosis of recurrent and unresectable or metastatic
HNSCC.

- Hepatocellular Carcinoma (HCC)

- Any radiographic or histologic documentation of locally advanced or metastatic
HCC.

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

- Histologically or cytologically confirmed diagnosis of NSCLC.

- Must not have progressed on or within 6 months of completing adjuvant PD-L1 therapy.

- Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase
(ALK) genomic tumor aberrations are excluded

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 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

- Use of immune suppressive agents

- 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.

- Chemotherapy or biological therapy within 28 days of therapy. Targeted therapy (e.g.,
tyrosine kinase inhibitors) within 14 days of enrollment

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

- Additional criteria may apply.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Anumeha Gupta, MD

Role: Study Director

Affiliation: Nektar Therapeutics

Overall Contact

Name: Nektar Recruitment

Phone: 855-482-8676

Email: StudyInquiry@nektar.com

Locations

Facility Status Contact
Investigator Site - San Francisco
San Francisco, California 94115
United States
Recruiting
Investigator Site - Denver
Aurora, Colorado 80045
United States
Recruiting
Investigator Site - New Orleans
New Orleans, Louisiana 70816
United States
Recruiting
Investigator Site -Minneapolis
Minneapolis, Minnesota 55426
United States
Recruiting
Investigator Site - Billings
Billings, Montana 59101
United States
Recruiting
Investigator Site - Omaha
Omaha, Nebraska 68198
United States
Recruiting
Investigator Site - Las Vegas
Las Vegas, Nevada 89169
United States
Recruiting
Investigator Site - New Brunswick
New Brunswick, New Jersey 08901
United States
Recruiting
Investigator Site - New York
New York, New York 10003
United States
Recruiting
Investigator Site - New York
New York, New York 10032
United States
Recruiting
Investigator Site - Germantown
Memphis, Tennessee 38138
United States
Active, not recruiting
Investigator Site - Falls Church
Falls Church, Virginia 22042
United States
Recruiting
Investigator Site - Tacoma
Tacoma, Washington 98405
United States
Recruiting
Investigator Site - Milwaukee
Milwaukee, Wisconsin 53226
United States
Recruiting