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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04049617




Registration number
NCT04049617
Ethics application status
Date submitted
31/07/2019
Date registered
8/08/2019
Date last updated
6/03/2020

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Participants With Advanced Solid Tumors
Scientific title
A Phase 1b/2 Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
GS-US-494-5484
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GS-4224

Experimental: GS-4224 - Dose Escalation (Phase 1b):
Participants will be sequentially enrolled in a dose escalation design to receive GS-4224 starting at 400 mg. Subsequent doses of = 700 mg and = 1000 mg are planned based on safety and tolerability of each dose level.
Dose Expansion (Phase 2):
Dose expansion will begin when the RP2D has been determined.


Treatment: Drugs: GS-4224
Tablets administered orally once daily

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) During the Dose Escalation Phase - A DLT is any toxicity defined as follows excluding toxicities clearly related to disease progression or disease-related processes occurring during the DLT assessment window (Day 1 through Day 21):
Grade = 4 neutropenia
Grade = 3 neutropenia with fever
Grade = 3 thrombocytopenia
Grade = 2 bleeding
Grade = 3 anemia
Grade = 3 or higher non-hematologic toxicity (excluding Grade 3 nausea or emesis or Grade 3 diarrhea)
Grade = 2 non-hematologic treatment-emergent adverse event that in the opinion of the investigator is of potential clinical significance
Treatment interruption of = 7 days due to unresolved toxicity
Any toxicity event that precludes further administration of GS-4224
Any Grade 3 or Grade 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin lasting = 7 days
An immune-related adverse event (irAE) for which immunotherapy should be permanently discontinued
Timepoint [1] 0 0
Day 1 through Day 21
Secondary outcome [1] 0 0
Pharmacokinetic (PK) Parameter: Tlast of GS-4224 During the Dose Escalation Phase - Tlast is defined as the time (observed time point) of Clast.
Timepoint [1] 0 0
Predose and 0.5, 1, 1.5, 2.5, 4, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days)
Secondary outcome [2] 0 0
PK Parameter: Tmax of GS-4224 During the Dose Escalation Phase - Tmax is defined as the time (observed time point) of Cmax.
Timepoint [2] 0 0
Predose and 0.5, 1, 1.5, 2.5, 4, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days)
Secondary outcome [3] 0 0
PK Parameter: Cmax of GS-4224 During the Dose Escalation Phase - Cmax is defined as the maximum observed concentration of drug.
Timepoint [3] 0 0
Predose and 0.5, 1, 1.5, 2.5, 4, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days)
Secondary outcome [4] 0 0
PK Parameter: Ctau of GS-4224 During the Dose Escalation Phase - Ctau is defined as the observed drug concentration at the end of the dosing interval.
Timepoint [4] 0 0
Predose and 0.5, 1, 1.5, 2.5, 4, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days)
Secondary outcome [5] 0 0
PK Parameter: AUClast of GS-4224 During the Dose Escalation Phase - AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Timepoint [5] 0 0
Predose and 0.5, 1, 1.5, 2.5, 4, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days)
Secondary outcome [6] 0 0
PK Parameter: AUCtau of GS-4224 During the Dose Escalation Phase - AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Timepoint [6] 0 0
Predose and 0.5, 1, 1.5, 2.5, 4, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days)
Secondary outcome [7] 0 0
PK Parameter: t1/2 of GS-4224 During the Dose Escalation Phase - t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Timepoint [7] 0 0
Predose and 0.5, 1, 1.5, 2.5, 4, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days)
Secondary outcome [8] 0 0
Percentage of Participants Experiencing = Grade 3 Treatment-Emergent Adverse Events During the Dose Expansion Phase
Timepoint [8] 0 0
First dose date through end of treatment plus 30 days, approximately 5 years
Secondary outcome [9] 0 0
Percentage of Participants Experiencing = Grade 3 Treatment-Emergent Laboratory Abnormalities During the Dose Expansion Phase
Timepoint [9] 0 0
First dose date through end of treatment plus 30 days, approximately 5 years

Eligibility
Key inclusion criteria
Key

- Dose Escalation Cohorts: Histologically or cytologically confirmed advanced malignant
solid tumor that is refractory to or intolerant of all standard therapy or for which
no standard therapy is available.

- Dose Expansion Cohort: Individuals must have available sufficient and adequate
formalin fixed tumor sample preferably from a biopsy of a tumor lesion obtained either
at the time of or after the diagnosis of advanced disease has been made and from a
site not previously irradiated. Alternatively, individuals must agree to have a biopsy
taken prior to entering the study to provide adequate tissue.

- Dose Escalation Biopsy Substudy: Documented ligand 1 of programmed cell death protein
1 (PD-L1) expression in the tumor (tumor proportion score (TPS) > 10% or combined
positive score (CPS) > 10).

- Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.

- Adequate organ function.

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History or evidence of clinically significant disorder, condition, or disease that, in
the opinion of the Investigator or Medical Monitor would pose a risk to individual
safety or interfere with the study evaluations, procedures, or completion.

- Dose Escalation Cohorts: History of = Grade 3 Adverse Events (AEs) during prior
treatment with an immune checkpoint inhibitor, or history of discontinuation of
treatment with an immune checkpoint inhibitor due to AEs.

- Dose Expansion Cohort: Prior treatment with an immune checkpoint inhibitor (anti-PD-1,
anti-PD-L1, or anti- ligand 2 of programmed cell death protein 1 (PD-L2) antibodies).

- History of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, vascular thrombosis associated with
antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy,
Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis,
or glomerulonephritis).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Other
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)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
United States of America
State/province [2] 0 0
Washington
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are to characterize the safety and tolerability of
GS-4224 and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)
of GS-4224 in participants with advanced solid tumors.
Trial website
https://clinicaltrials.gov/show/NCT04049617
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Gilead Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-833-445-3230 (GILEAD-0)
Fax 0 0
Email 0 0
GileadClinicalTrials@gilead.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04049617