Clinical trial NCT04049617: Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Evixapodlin (Formerly GS-4224) in Participants With Advanced Solid Tumors
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-08-08
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed description: This was a planned Phase 1/2 study. However, Phase 2 was not conducted because the study was closed due to sponsor decision prior to opening the dose expansion cohort and hence, RP2D analysis was not performed.

Eligibility criteria: Key Inclusion Criteria:

* 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 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.

Primary outcomes:
measure: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) During the Dose Escalation Phase
timeFrame: Day 1 through Day 21
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter: AUCtau of Evixapodlin During the Dose Escalation Phase
timeFrame: 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
measure: PK Parameter: Cmax of Evixapodlin During the Dose Escalation Phase
timeFrame: Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
measure: PK Parameter: Ctrough of Evixapodlin During the Dose Escalation Phase
timeFrame: Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
measure: PK Parameter: Tmax of Evixapodlin During the Dose Escalation Phase
timeFrame: Intensive PK: Predose, 0.5, 1, 1.5, 2.5, 4, 6, 24 h postdose (400-1500 QD mg cohorts) on C1D1 & D15
measure: Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Adverse Events During the Dose Expansion Phase
timeFrame: First dose date through end of treatment plus 30 days, approximately 5 years
measure: Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Laboratory Abnormalities During the Dose Expansion Phase
timeFrame: First dose date through end of treatment plus 30 days, approximately 5 years
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Care Associates for Research and Excellence Inc
state: California
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust, LLC
city: Grafton, Auckland
country: New Zealand
facility: Auckland Clinical Studies Ltd
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: