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

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Evixapodlin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04049617

2019-004605-27 (EudraCT Number)

GS-US-494-5484

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 9 patient groups

Cohort 1: Evixapodlin 400 mg (Phase 1)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin

Cohort 2: Evixapodlin 700 mg (Phase 1)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin

Cohort 3: Evixapodlin 1000 mg (Phase 1)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin

Cohort 4: Evixapodlin 1500 mg (Phase 1)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin

Cohort 5: Evixapodlin 1000 mg (Phase 1)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin

Cohort 1 Substudy: Evixapodlin 400 mg (Phase 1)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin

Cohort 2 Substudy: Evixapodlin 700 mg (Phase 1)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin

Cohort 3 Substudy: Evixapodlin 1000 mg (Phase 1)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin

Dose Expansion (Phase 2)

Experimental group

Description:

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

Treatment:

Drug: Evixapodlin