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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03138889
Ethics application status
Date submitted
1/05/2017
Date registered
3/05/2017
Date last updated
26/04/2021

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
Melanoma 0 0
Urothelial Carcinoma 0 0
Head and Neck Squamous Cell Carcinoma 0 0
Hepatocellular Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Liver
Cancer 0 0 0 0
Head and neck

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

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


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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®) - Safety and Tolerability of NKTR-214 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.
Timepoint [1] 0 0
100 days after last dose
Primary outcome [2] 0 0
Recommended Phase 2 Dose (RP2D) or Maximum Tolerated Dose (MTD) or optimal dosing schedule of NKTR-214 in combination with pembrolizumab (Keytruda®) - To define the Recommended Phase 2 Dose (RP2D), or Maximum Tolerated Dose (MTD), or optimal dosing schedule of NKTR-214 in combination with pembrolizumab (Keytruda®), by evaluating the incidence of Dose Limiting Toxicities (DLTs) within the DLT window (21 days after first dose), drug-related AEs, SAEs, adverse events leading to discontinuation, deaths and overall tolerability.
Timepoint [2] 0 0
100 days after last dose
Primary outcome [3] 0 0
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 - ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR
Timepoint [3] 0 0
100 days after last dose
Secondary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 plus pembrolizumab (Keytruda®) with or without systemic chemotherapy in untreated metastatic NSCLC. - Safety and Tolerability of NKTR-214 plus pembrolizumab (Keytruda®) with or without systemic chemotherapy as evaluated by incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation, deaths, and overall tolerability.
Timepoint [1] 0 0
100 days after last dose
Secondary outcome [2] 0 0
Objective response rate (ORR) per RECIST 1.1 in Dose Optimization - ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR
Timepoint [2] 0 0
Through study completion, an expected average of 2 years
Secondary outcome [3] 0 0
Duration of response (DOR) - DOR for patients who have confirmed complete response (CR) or confirmed partial response (PR) as the date from first documented CR or PR to the date of the first objectively documented disease progression per RECIST 1.1 or death due to any cause, whichever is earlier.
Timepoint [3] 0 0
Through study completion, an expected average of 2 years
Secondary outcome [4] 0 0
Clinical benefit rate (CBR) - CBR is defined as the number of patients with confirmed complete response, confirmed partial response, or stable disease (= 7 weeks).
Timepoint [4] 0 0
Through study completion, an expected average of 2 years
Secondary outcome [5] 0 0
Time to Response (TTR) - TTR will be defined for patients who had confirmed CR or confirmed PR as the time from the date of first dose to date of first documented CR or PR per RECIST 1.1.
Timepoint [5] 0 0
Through study completion, an expected average of 2 years
Secondary outcome [6] 0 0
Progression-Free Survival (PFS) - PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause
Timepoint [6] 0 0
Through study completion, an expected average of 2 years
Secondary outcome [7] 0 0
Overall Survival (OS) - OS is defined as the time from date of first dose to the date of death.
Timepoint [7] 0 0
Through study completion, an expected average of 2 years
Secondary outcome [8] 0 0
To assess the association between efficacy measures and PD L1 expression in tumors. - Efficacy measures are defined as ORR and changes in PD-L1 expression from on treatment biopsy in Dose Optimization.
Timepoint [8] 0 0
Through study completion, an expected average 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 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
Minimum age
18 Years
Maximum age
No limit
Gender
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
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Investigator Site - Richmond - 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
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Montana
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
United States of America
State/province [23] 0 0
Wisconsin
Country [24] 0 0
France
State/province [24] 0 0
Créteil
Country [25] 0 0
France
State/province [25] 0 0
Marseille
Country [26] 0 0
France
State/province [26] 0 0
Rennes
Country [27] 0 0
France
State/province [27] 0 0
Saint Quentin
Country [28] 0 0
France
State/province [28] 0 0
Toulouse
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Gauting
Country [31] 0 0
Germany
State/province [31] 0 0
Gerlingen
Country [32] 0 0
Germany
State/province [32] 0 0
Grosshansdorf
Country [33] 0 0
Germany
State/province [33] 0 0
Hemer
Country [34] 0 0
Germany
State/province [34] 0 0
Lübeck
Country [35] 0 0
Italy
State/province [35] 0 0
Lucca
Country [36] 0 0
Italy
State/province [36] 0 0
Monza
Country [37] 0 0
Spain
State/province [37] 0 0
Barcelona
Country [38] 0 0
Spain
State/province [38] 0 0
Las Palmas De Gran Canaria
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 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 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.
Trial website
https://clinicaltrials.gov/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
Nektar Recruitment
Address 0 0
Country 0 0
Phone 0 0
855-482-8676
Fax 0 0
Email 0 0
StudyInquiry@nektar.com
Contact person for scientific queries

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