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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03138889




Registration number
NCT03138889
Ethics application status
Date submitted
1/05/2017
Date registered
3/05/2017
Date last updated
10/03/2023

Titles & IDs
Public title
Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally Advanced or Metastatic Solid Tumors
Scientific 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
Secondary ID [1] 0 0
16-214-05
Universal Trial Number (UTN)
Trial acronym
PROPEL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NKTR-214
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - NKTR-214
Treatment: Drugs - NKTR-214
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin
Treatment: Drugs - Nab paclitaxel
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Atezolizumab

Experimental: Dose Optimization, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) - Cohort 1: NKTR-214 will be combined with pembrolizumab

Experimental: Dose Expansion, Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) - Cohort 2: NKTR-214 will be combined with pembrolizumab

Experimental: Dose Expansion, Combo of NKTR-214 + Pembrolizumab (KEYTRUDA®) - Cohort 3: NKTR-214 will be combined with pembrolizumab

Experimental: Dose Expansion, NKTR-214 + Pembrolizumab and either Cisplatin, or Carboplatin and Pemetrexed - Cohort 4: NKTR-214 will be dosed in combination with pembrolizumab and either cisplatin, or carboplatin and pemetrexed, per investigator discretion

Experimental: Dose Expansion, NKTR-214 + Pembrolizumab and Carboplatin and either Nab-paclitaxel or Paclitaxel - Cohort 5: NKTR-214 will be dosed in combination with pembrolizumab and carboplatin and either nab-paclitaxel or paclitaxel, per investigator discretion

Experimental: Combo of NKTR-214 + Pembrolizumab(KEYTRUDA®) or Atezolizumab (TECENTRIQ®) - Cohort 0 (Before Protocol Amendment 5.0): NKTR-214 will be combined with pembrolizumab or atezolizumab


Treatment: Drugs: 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.

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

Treatment: Drugs: NKTR-214
NKTR-214: The dose will be 0.006 mg/kg intravenous (IV) infusion.

Treatment: Drugs: NKTR-214
NKTR-214: The dose will be 0.010 mg/kg intravenous (IV) infusion.

Treatment: Drugs: Cisplatin
Cisplatin will be dosed per the pharmacy manual

Treatment: Drugs: Carboplatin
Carboplatin will be dosed per the pharmacy manual

Treatment: Drugs: Nab paclitaxel
Nab-paclitaxel will be dosed per local practice and label

Treatment: Drugs: Paclitaxel
Paclitaxel will be dosed per local practice and label

Treatment: Drugs: Pemetrexed
Pemetrexed will be dosed per the pharmacy manual

Treatment: Drugs: Atezolizumab
Atezolizumab will be dosed per current label indication
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Experiencing Dose-Limiting Toxicities in Dose Optimization Cohort 1a
Timepoint [1] 0 0
DLTs were assessed at 21 days from Cycle 1
Primary outcome [2] 0 0
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] for Dose Optimization Cohort 1a.
Timepoint [2] 0 0
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 outcome [3] 0 0
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.
Timepoint [3] 0 0
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 outcome [4] 0 0
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.
Timepoint [4] 0 0
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.

Eligibility
Key inclusion criteria
Dose Optimization and Dose Expansion

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/08/2022
Sample size
Target
Accrual to date
Final
162
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Epworth HealthCare - Richmond
Recruitment postcode(s) [1] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Montana
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
Nevada
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
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New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
United States of America
State/province [20] 0 0
Wisconsin
Country [21] 0 0
France
State/province [21] 0 0
Saint Quentin
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Germany
State/province [23] 0 0
Gauting
Country [24] 0 0
Germany
State/province [24] 0 0
Grosshansdorf
Country [25] 0 0
Germany
State/province [25] 0 0
Hemer
Country [26] 0 0
Germany
State/province [26] 0 0
Lübeck
Country [27] 0 0
Germany
State/province [27] 0 0
Stuttgart
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Las Palmas De Gran Canaria
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Spain
State/province [31] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Nektar Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03138889
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Nektar Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03138889