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.
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
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 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
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):
- Histologically confirmed stage III (unresectable) or stage IV (metastatic)
- 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
- Head and Neck Squamous Cell Carcinoma (HNSCC)
- Histologically confirmed diagnosis of recurrent and unresectable or metastatic
- Hepatocellular Carcinoma (HCC)
- Any radiographic or histologic documentation of locally advanced or metastatic
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
- 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
- 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.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Anumeha Gupta, MD
Role: Study Director
Affiliation: Nektar Therapeutics
Name: Nektar Recruitment
|Investigator Site - San Francisco
San Francisco, California 94115
|Investigator Site - Denver
Aurora, Colorado 80045
|Investigator Site - New Orleans
New Orleans, Louisiana 70816
|Investigator Site -Minneapolis
Minneapolis, Minnesota 55426
|Investigator Site - Billings
Billings, Montana 59101
|Investigator Site - Omaha
Omaha, Nebraska 68198
|Investigator Site - Las Vegas
Las Vegas, Nevada 89169
|Investigator Site - New Brunswick
New Brunswick, New Jersey 08901
|Investigator Site - New York
New York, New York 10003
|Investigator Site - New York
New York, New York 10032
|Investigator Site - Germantown
Memphis, Tennessee 38138
|Active, not recruiting|
|Investigator Site - Falls Church
Falls Church, Virginia 22042
|Investigator Site - Tacoma
Tacoma, Washington 98405
|Investigator Site - Milwaukee
Milwaukee, Wisconsin 53226