Clinical trial NCT03138889: Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: NKTR-214
Metastatic Non-Small Cell Lung Cancer
Pembrolizumab
Keytruda®
NSCLC
Bempegaldesleukin
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-05-03
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 included first-line and second-line advanced or metastatic solid tumors including non-small cell lung cancer (NSCLC)

The dose expansion cohort will include first-line NSCLC patients.

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 evaluated an every three-week dose regimen (q3w) of NKTR-214 in combination with pembrolizumab 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.

Dose Expansion: NKTR-214 in combination with pembrolizumab 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.

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 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

Primary outcomes:
measure: Number of Participants Experiencing Dose-Limiting Toxicities in Dose Optimization Cohort 1a
timeFrame: DLTs were assessed at 21 days from Cycle 1
measure: Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] for Dose Optimization Cohort 1a.
timeFrame: AEs reported starting immediately after first dose of study drug(s) until 100 days after the last dose of all study drugs, up to approximately 28 months.
measure: Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by RECIST 1.1 of NKTR-214 Plus Pembrolizumab for Dose Expansion Cohorts 2 and 3.
timeFrame: Until disease progression, death, unacceptable toxicity, symptomatic deterioration, Investigator's decision to discontinue treatment, patient withdrew consent or lost to follow-up, or study terminated by Sponsor; or until maximum of 2 years.
measure: Objective Response Rate (ORR) Per Investigator's Assessment by RECIST 1.1 of NKTR-214 at a Dose of 0.006 mg/kg With Pembrolizumab and Platinum-based Chemotherapy for Dose Expansion Cohorts 4+5.
timeFrame: Until disease progression, death, unacceptable toxicity, symptomatic deterioration, Investigator's decision to discont. treatment, patient withdrew consent or lost to follow-up, or study terminated by Sponsor; or until maximum of 2 years.
Secondary outcomes:
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group, PA - North Hills
state: Arkansas
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Augusta
country: United States
facility: Augusta University - Augusta University Medical Center
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis Park
country: United States
facility: Park Nicollet - Frauenshuh Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
state: Nevada
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke Clinical Research Institute
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Inova Melanoma and Skin Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Milwaukee
country: United States
facility: Froedtert & the Medical College of Wisconsin Froedtert Hospital
state: Wisconsin
city: Richmond
country: Australia
facility: Epworth HealthCare
state: Victoria
city: Saint Quentin
country: France
facility: Centre Hospitalier de Saint-Quentin
city: Berlin
country: Germany
facility: Vivantes Klinikum Spandau
city: Gauting
country: Germany
facility: Asklepios Fachkliniken München-Gauting
city: Grosshansdorf
country: Germany
facility: LungenClinic Grosshansdorf
city: Hemer
country: Germany
facility: Lungenklinik Hemer
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario Insular de Gran Canaria
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: HM Universitario Sanchinarro
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
Study officials:
affiliation: Nektar Therapeutics
name: Study Director
role: STUDY_DIRECTOR
References: