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Brief Title: Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally Advanced or Metastatic Solid Tumors

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

INTRODUCTION

  • Org Study ID: 16-214-05
  • Secondary ID: N/A
  • NTC ID: NCT03138889
  • Sponsor: 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®) 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.

  • Overall Status
    Recruiting
  • Start Date
    June 9, 2017
  • Phase
    Phase 1, Phase 2
  • Study Type
    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 - Timeframe: 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 - Timeframe: 100 days after last dose

Primary Outcome 3 - Measure: Objective response rate (ORR) per blinded independent central review (BICR) by RECIST 1.1 of NKTR-214 plus pembrolizumab with or without systemic chemotherapy in patients with untreated metastatic NSCLC

Primary Outcome 3 - Timeframe: 100 days after last dose

CONDITION

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

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Study Director

Role: Study Director

Affiliation: Nektar Therapeutics

Overall Contact

Name: Study Director

Phone: 855-482-8676

Email: StudyInquiry@nektar.com, medicalaffairs@nektar.com

LOCATION

Facility Status Contact
Facility: Highlands Oncology Group, PA - North Hills
Fayetteville, Arkansas 72703
United States
Status: Recruiting Contact: N/A
Facility: University of Colorado Anschutz Medical Campus
Aurora, Colorado 80045
United States
Status: Recruiting Contact: N/A
Facility: Florida Hospital Cancer Institute
Orlando, Florida 32804
United States
Status: Recruiting Contact: N/A
Facility: Emory University School of Medicine
Atlanta, Georgia 30322
United States
Status: Recruiting Contact: N/A
Facility: Augusta University - Augusta University Medical Center
Augusta, Georgia 30912
United States
Status: Recruiting Contact: N/A
Facility: Southern Illinois University (SIU) School of Medicine
Springfield, Illinois 62702
United States
Status: Recruiting Contact: N/A
Facility: University of Kansas Medical Center (KUMC)
Kansas City, Kansas 66160
United States
Status: Recruiting Contact: N/A
Facility: Ochsner Medical Center
New Orleans, Louisiana 70816
United States
Status: Recruiting Contact: N/A
Facility: Henry Ford Hospital
Detroit, Michigan 48202
United States
Status: Recruiting Contact: N/A
Facility: St. Vincent Frontier Cancer Center
Billings, Montana 59101
United States
Status: Recruiting Contact: N/A
Facility: University of Nebraska Medical Center
Omaha, Nebraska 68198
United States
Status: Recruiting Contact: N/A
Facility: New York University Langone Medical Center
New York, New York 10016
United States
Status: Recruiting Contact: N/A
Facility: Duke Clinical Research Institute
Durham, North Carolina 27705
United States
Status: Recruiting Contact: N/A
Facility: Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
United States
Status: Recruiting Contact: N/A
Facility: Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)
Nashville, Tennessee 37203
United States
Status: Recruiting Contact: N/A
Facility: The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A
Facility: Inova Melanoma and Skin Cancer Center
Fairfax, Virginia 22031
United States
Status: Recruiting Contact: N/A
Facility: Centre Hospitalier Intercommunal de Créteil
Créteil, 94010
France
Status: Recruiting Contact: N/A
Facility: CHU Hôpital de la Timone
Marseille, 13385
France
Status: Recruiting Contact: N/A
Facility: CHU de Rennes - Hôpital Pontchaillou
Rennes, 35033
France
Status: Recruiting Contact: N/A
Facility: Centre Hospitalier de Saint-Quentin
Saint Quentin, 2100
France
Status: Recruiting Contact: N/A
Facility: Hôpital Larrey
Toulouse, 31059
France
Status: Recruiting Contact: N/A
Facility: LungenClinic Grosshansdorf
Grosshansdorf, 22927
Germany
Status: Recruiting Contact: N/A
Facility: Universitätsklinikum Schleswig-Holstein
Lübeck, 23538
Germany
Status: Recruiting Contact: N/A
Facility: Robert-Bosch-Krankenhaus
Stuttgart, 70376
Germany
Status: Recruiting Contact: N/A
Facility: Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Universitario Vall d'Hebron
Barcelona, 08035
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Universitario Insular de Gran Canaria
Las Palmas De Gran Canaria, 35016
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Clínico San Carlos
Madrid, 28040
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Spain
Status: Recruiting Contact: N/A
Facility: HM Universitario Sanchinarro
Madrid, 28050
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Universitari i Politècnic La Fe
Valencia, 46026
Spain
Status: Recruiting Contact: N/A