Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Evixapodlin (Formerly GS-4224) in Participants With Advanced Solid Tumors

NCT ID: NCT04049617

Last Updated: 2022-10-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-26
• Study Completion Date: 2021-03-30

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Evixapodlin 400 mg (Phase 1)

Participants will receive Evixapodlin 400 mg once daily for 21 days of each cycle.

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Cohort 2: Evixapodlin 700 mg (Phase 1)

Participants will receive Evixapodlin 700 mg once daily for 21 days of each cycle.

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Cohort 3: Evixapodlin 1000 mg (Phase 1)

Participants will receive Evixapodlin 1000 mg once daily for 21 days of each cycle.

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Cohort 4: Evixapodlin 1500 mg (Phase 1)

Participants will receive Evixapodlin 1500 mg once daily for 21 days of each cycle.

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Cohort 5: Evixapodlin 1000 mg (Phase 1)

Participants are planned to receive Evixapodlin 1000 mg twice daily (BID) for 21 days of each cycle.

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Cohort 1 Substudy: Evixapodlin 400 mg (Phase 1)

Participants will receive Evixapodlin 400 mg once daily for 21 days of each cycle.

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Cohort 2 Substudy: Evixapodlin 700 mg (Phase 1)

Participants are planned to receive Evixapodlin 700 mg once daily for 21 days of each cycle.

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Cohort 3 Substudy: Evixapodlin 1000 mg (Phase 1)

Participants will receive Evixapodlin 1000 mg once daily for 21 days of each cycle.

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Dose Expansion (Phase 2)

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

Group Type: EXPERIMENTAL

Evixapodlin

Intervention Type: DRUG

Tablets administered orally.

Interventions

Evixapodlin

Tablets administered orally.

Intervention Type: DRUG

Other Intervention Names

GS-4224

Eligibility Criteria

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.

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

California Care Associates for Research and Excellence Inc

Encinitas, California, United States

NEXT Oncology

San Antonio, Texas, United States

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States

Auckland City Hospital

Auckland, , New Zealand

Christchurch Clinical Studies Trust, LLC

Christchurch, , New Zealand

Auckland Clinical Studies Ltd

Grafton, Auckland, , New Zealand

Countries

United States; New Zealand

References

Odegard JM, Othman AA, Lin KW, Wang AY, Nazareno J, Yoon OK, Ling J, Lad L, Dunbar PR, Thai D, Ang E, Waldron N, Deva S. Oral PD-L1 inhibitor GS-4224 selectively engages PD-L1 high cells and elicits pharmacodynamic responses in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 11;12(4):e008547. doi: 10.1136/jitc-2023-008547.

Reference Type: DERIVED

PMID: 38604815 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-004605-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-494-5484

Identifier Type: -

Identifier Source: org_study_id