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

Non-Small Cell Lung Cancer Clinical Trial

— PROPEL  

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03138889
• Other study ID #: 16-214-05
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 9, 2017
• Est. completion date: August 24, 2022

Study information

• Verified date: March 2023
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 162
• Est. completion date: August 24, 2022
• Est. primary completion date: July 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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 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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Small Cell Lung Cancer

Intervention

Drug:
• NKTR-214
NKTR-214: The dose will be 0.008 mg/kg intravenous (IV) infusion administered over 30 (± 5) minutes q3w. The maximum dose of NKTR-214 will be 0.012 mg/kg. This will include a fixed 3+3 dose escalation followed by intra-patient step-up dose escalation based on tolerability.
• Pembrolizumab
Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.
• NKTR-214
NKTR-214: The dose will be 0.006 mg/kg intravenous (IV) infusion.
• NKTR-214
NKTR-214: The dose will be 0.010 mg/kg intravenous (IV) infusion.
• Cisplatin
Cisplatin will be dosed per the pharmacy manual
• Carboplatin
Carboplatin will be dosed per the pharmacy manual
• Nab paclitaxel
Nab-paclitaxel will be dosed per local practice and label
• Paclitaxel
Paclitaxel will be dosed per local practice and label
• Pemetrexed
Pemetrexed will be dosed per the pharmacy manual
• Atezolizumab
Atezolizumab will be dosed per current label indication

Locations

Country	Name	City	State
Australia	Epworth HealthCare	Richmond	Victoria
France	Centre Hospitalier de Saint-Quentin	Saint Quentin
Germany	Vivantes Klinikum Spandau	Berlin
Germany	Asklepios Fachkliniken München-Gauting	Gauting
Germany	LungenClinic Grosshansdorf	Grosshansdorf
Germany	Lungenklinik Hemer	Hemer
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Insular de Gran Canaria	Las Palmas De Gran Canaria
Spain	HM Universitario Sanchinarro	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United States	Augusta University - Augusta University Medical Center	Augusta	Georgia
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke Clinical Research Institute	Durham	North Carolina
United States	Inova Melanoma and Skin Cancer Center	Fairfax	Virginia
United States	Highlands Oncology Group, PA - North Hills	Fayetteville	Arkansas
United States	West Cancer Center	Germantown	Tennessee
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada
United States	Froedtert & the Medical College of Wisconsin Froedtert Hospital	Milwaukee	Wisconsin
United States	Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Blue Ridge Cancer Care	Roanoke	Virginia
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	Park Nicollet - Frauenshuh Cancer Center	Saint Louis Park	Minnesota
United States	California Pacific Medical Center	San Francisco	California
United States	Northwest Medical Specialties	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Nektar Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Dose-Limiting Toxicities in Dose Optimization Cohort 1a	DLTs were assesses in the Dose Optimization Cohort 1 a, which had doses of NKTR-214 as 0.008 mg/kg, 0.010 mg/kg, and 0.012 m/kg, I combination with pembrolizumab at 200 mg.; A single DLT (hypotension) was reported in 1 patient in dose optimization Cohort 1a.	DLTs were assessed at 21 days from Cycle 1
Primary	Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] for Dose Optimization Cohort 1a.	Safety and Tolerability of NKTR-214 (starting at dose of 0.008 mg/kg) 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.	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.
Primary	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.	ORR per BICR by RECIST 1.1 for the Response Evaluable Population dose expansion Cohorts 2 and 3.; ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.; The Response Evaluable Population was subjects who received at least 1 dose (or partial dose) of study drug, had measurable disease (per RECIST 1.1) at baseline, and had at least 1 post-baseline assessment of tumor response.	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.
Primary	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.	ORR per Investigator's Assessment* by RECIST 1.1 for the Response Evaluable Population dose expansion Cohorts 4 +5. The Response Evaluable Population was subjects who received at least 1 dose (or partial dose) of study drug, had measurable disease (per RECIST 1.1) at baseline, and had at least 1 post-baseline assessment of tumor response.; Objective response is the sum of confirmed complete response and confirmed partial response.; *Efficacy endpoint for Cohort 4 +5 is per Investigator's Assessment due to the early termination of the study and incompleteness of BICR data for these cohorts.	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.