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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04049617
Ethics application status
Date submitted
31/07/2019
Date registered
8/08/2019

Titles & IDs
Public title
Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Evixapodlin (Formerly 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
2019-004605-27
Secondary ID [2] 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 - Evixapodlin

Experimental: Cohort 1: Evixapodlin 400 mg (Phase 1) - Participants will receive Evixapodlin 400 mg once daily for 21 days of each cycle.

Experimental: Cohort 2: Evixapodlin 700 mg (Phase 1) - Participants will receive Evixapodlin 700 mg once daily for 21 days of each cycle.

Experimental: Cohort 3: Evixapodlin 1000 mg (Phase 1) - Participants will receive Evixapodlin 1000 mg once daily for 21 days of each cycle.

Experimental: Cohort 4: Evixapodlin 1500 mg (Phase 1) - Participants will receive Evixapodlin 1500 mg once daily for 21 days of each cycle.

Experimental: Cohort 5: Evixapodlin 1000 mg (Phase 1) - Participants are planned to receive Evixapodlin 1000 mg twice daily (BID) for 21 days of each cycle.

Experimental: Cohort 1 Substudy: Evixapodlin 400 mg (Phase 1) - Participants will receive Evixapodlin 400 mg once daily for 21 days of each cycle.

Experimental: Cohort 2 Substudy: Evixapodlin 700 mg (Phase 1) - Participants are planned to receive Evixapodlin 700 mg once daily for 21 days of each cycle.

Experimental: Cohort 3 Substudy: Evixapodlin 1000 mg (Phase 1) - Participants will receive Evixapodlin 1000 mg once daily for 21 days of each cycle.

Experimental: Dose Expansion (Phase 2) - Dose expansion is planned to begin when the recommended Phase 2 dose (RP2D) will be determined.


Treatment: Drugs: Evixapodlin
Tablets administered orally.
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 (DLTs) During the Dose Escalation Phase
Timepoint [1] 0 0
Day 1 through Day 21
Secondary outcome [1] 0 0
Pharmacokinetic (PK) Parameter: AUCtau of Evixapodlin During the Dose Escalation Phase
Timepoint [1] 0 0
Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 hours (h) postdose (400-1500 once daily [QD] mg cohorts) on Cycle (C) 1 Day (D) 1 & D15
Secondary outcome [2] 0 0
PK Parameter: Cmax of Evixapodlin During the Dose Escalation Phase
Timepoint [2] 0 0
Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
Secondary outcome [3] 0 0
PK Parameter: Ctrough of Evixapodlin During the Dose Escalation Phase
Timepoint [3] 0 0
Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
Secondary outcome [4] 0 0
PK Parameter: Tmax of Evixapodlin During the Dose Escalation Phase
Timepoint [4] 0 0
Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
Secondary outcome [5] 0 0
Percentage of Participants Experiencing = Grade 3 Treatment-Emergent Adverse Events During the Dose Expansion Phase
Timepoint [5] 0 0
First dose date through end of treatment plus 30 days, approximately 5 years
Secondary outcome [6] 0 0
Percentage of Participants Experiencing = Grade 3 Treatment-Emergent Laboratory Abnormalities During the Dose Expansion Phase
Timepoint [6] 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 and 1000 mg twice a day (BID) Dose Escalation Cohorts: 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. For the 1000 mg BID dose escalation cohort, individuals with melanoma, Merkel cell, microsatellite instability-high (MSI-H) cancers, and classical Hodgkin lymphoma (cHL) are not required to have archival or fresh biopsy tissue.
* Dose Escalation Biopsy Substudy and 1000 mg BID Dose Escalation Cohorts: 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). In the 1000 mg BID Cohort, PD-L1 expression will not be required for Merkel cell, melanoma, MSI-H cancers, and cHL.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
* Adequate organ function.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
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 Escalation 1000 mg BID and 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
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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/03/2021
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
United States of America
State/province [3] 0 0
Washington
Country [4] 0 0
New Zealand
State/province [4] 0 0
Auckland
Country [5] 0 0
New Zealand
State/province [5] 0 0
Christchurch
Country [6] 0 0
New Zealand
State/province [6] 0 0
Grafton, Auckland

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04049617