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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/NCT04049617




Registration number
NCT04049617
Ethics application status
Date submitted
31/07/2019
Date registered
8/08/2019
Date last updated
6/10/2022

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
Terminated
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
The primary objectives of this study are to characterize the safety and tolerability of
evixapodlin (formerly GS-4224) and to determine the maximum tolerated dose (MTD) and
recommended phase 2 dose (RP2D) of evixapodlin in participants with advanced solid tumors.
Trial website
https://clinicaltrials.gov/ct2/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
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/NCT04049617