The primary objectives of this study are to characterize the safety and tolerability of
GS-4224 and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)
of GS-4224 in participants with advanced solid tumors.
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 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,
Note: Other protocol defined Inclusion/Exclusion criteria may apply.