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

NCT03138889 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 16-214-05
• Study Type: interventional
• Target: 162
• Locations: 5 countries
• Sites: 38

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

NKTR-214; Metastatic Non-Small Cell Lung Cancer; Pembrolizumab; Keytruda®; NSCLC; Bempegaldesleukin

Outcome Measures

Primary Outcomes (4)

• 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

• 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.

• 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.

• 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.

Study Arms (6)

Dose Optimization, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)

EXPERIMENTAL

Cohort 1: NKTR-214 will be combined with pembrolizumab

Drug: NKTR-214; Drug: Pembrolizumab

Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)

EXPERIMENTAL

Cohort 2: NKTR-214 will be combined with pembrolizumab

Drug: Pembrolizumab; Drug: NKTR-214

Dose Expansion, Combo of NKTR-214 + Pembrolizumab (KEYTRUDA®)

EXPERIMENTAL

Cohort 3: NKTR-214 will be combined with pembrolizumab

Drug: Pembrolizumab; Drug: NKTR-214

Dose Expansion, NKTR-214 + Pembrolizumab and either Cisplatin, or Carboplatin and Pemetrexed

EXPERIMENTAL

Cohort 4: NKTR-214 will be dosed in combination with pembrolizumab and either cisplatin, or carboplatin and pemetrexed, per investigator discretion

Drug: Pembrolizumab; Drug: NKTR-214; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

Dose Expansion, NKTR-214 + Pembrolizumab and Carboplatin and either Nab-paclitaxel or Paclitaxel

EXPERIMENTAL

Cohort 5: NKTR-214 will be dosed in combination with pembrolizumab and carboplatin and either nab-paclitaxel or paclitaxel, per investigator discretion

Drug: Pembrolizumab; Drug: NKTR-214; Drug: Carboplatin; Drug: Nab paclitaxel; Drug: Paclitaxel

Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) or Atezolizumab (TECENTRIQ®)

EXPERIMENTAL

Cohort 0 (Before Protocol Amendment 5.0): NKTR-214 will be combined with pembrolizumab or atezolizumab

Drug: Pembrolizumab; Drug: NKTR-214; Drug: Atezolizumab

Interventions

NKTR-214 DRUG

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.

Also known as: CD122-Biased Cytokine

Dose Optimization, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)

Pembrolizumab DRUG

Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

Also known as: Keytruda®

Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) or Atezolizumab (TECENTRIQ®); Dose Expansion, Combo of NKTR-214 + Pembrolizumab (KEYTRUDA®); Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®); Dose Expansion, NKTR-214 + Pembrolizumab and Carboplatin and either Nab-paclitaxel or Paclitaxel; Dose Expansion, NKTR-214 + Pembrolizumab and either Cisplatin, or Carboplatin and Pemetrexed; Dose Optimization, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®)

Cisplatin DRUG

Cisplatin will be dosed per the pharmacy manual

Also known as: Platinol®

Dose Expansion, NKTR-214 + Pembrolizumab and either Cisplatin, or Carboplatin and Pemetrexed

Carboplatin DRUG

Carboplatin will be dosed per the pharmacy manual

Also known as: Paraplatin®

Dose Expansion, NKTR-214 + Pembrolizumab and Carboplatin and either Nab-paclitaxel or Paclitaxel; Dose Expansion, NKTR-214 + Pembrolizumab and either Cisplatin, or Carboplatin and Pemetrexed

Nab paclitaxel DRUG

Nab-paclitaxel will be dosed per local practice and label

Also known as: Abraxane®

Dose Expansion, NKTR-214 + Pembrolizumab and Carboplatin and either Nab-paclitaxel or Paclitaxel

Paclitaxel DRUG

Paclitaxel will be dosed per local practice and label

Also known as: Taxol®

Dose Expansion, NKTR-214 + Pembrolizumab and Carboplatin and either Nab-paclitaxel or Paclitaxel

Pemetrexed DRUG

Pemetrexed will be dosed per the pharmacy manual

Also known as: Alimta®

Dose Expansion, NKTR-214 + Pembrolizumab and either Cisplatin, or Carboplatin and Pemetrexed

Atezolizumab DRUG

Atezolizumab will be dosed per current label indication

Also known as: Tecentriq®

Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) or Atezolizumab (TECENTRIQ®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nektar Therapeutics: lead

Study Sites (38)

Highlands Oncology Group, PA - North Hills

Fayetteville, Arkansas, 72703, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Augusta University - Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70816, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Park Nicollet - Frauenshuh Cancer Center

Saint Louis Park, Minnesota, 55426, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63156, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59101, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

Las Vegas, Nevada, 89169, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke Clinical Research Institute

Durham, North Carolina, 27705, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Inova Melanoma and Skin Cancer Center

Fairfax, Virginia, 22031, United States

Location

Blue Ridge Cancer Care

Roanoke, Virginia, 24153, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Froedtert & the Medical College of Wisconsin Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Epworth HealthCare

Richmond, Victoria, 3121, Australia

Location

Centre Hospitalier de Saint-Quentin

Saint-Quentin, 2100, France

Location

Vivantes Klinikum Spandau

Berlin, 13585, Germany

Location

Asklepios Fachkliniken München-Gauting

Gauting, 82131, Germany

Location

LungenClinic Grosshansdorf

Großhansdorf, 22927, Germany

Location

Lungenklinik Hemer

Hemer, 58675, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, 35016, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

HM Universitario Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

bempegaldesleukin; pembrolizumab; Cisplatin; Carboplatin; Taxes; Albumin-Bound Paclitaxel; Paclitaxel; Pemetrexed; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Economics; Health Care Economics and Organizations; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Study Director
• Organization: Nektar Therapeutics

StudyInquiry@nektar.com

855-482-8676

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: May 3, 2017
• Study Start: June 9, 2017
• Primary Completion: July 5, 2022
• Study Completion: August 24, 2022
• Last Updated: March 10, 2023
• Results First Posted: March 9, 2023

Record last verified: 2023-03

Locations

ES (7); FR (1); DE (6); AU (1); US (23)