Solid Tumor
Conditions
Brief summary
The goals of this clinical study are to identify if GS-4528 alone or in combination with anti-programmed cell death protein 1 (PD-1) (Anti-PD-1) Monoclonal Antibody is safe and tolerable in people with solid tumors and to identify the recommended dose of GS-4528 for further development that is safe to give to people alone or in combination with Anti-PD-1 Monoclonal Antibody. The primary objectives of this study are: * To assess the safety and tolerability of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody in participants with advanced solid tumors. * To identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and/or the recommended Phase 2 dose (RP2D) of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody in participants with advanced solid tumors.
Interventions
BIOLOGICALGS-4528
Administered intravenously
DRUGZimberelimab
Administered intravenously.
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documented disease: * Phase 1a dose escalation and backfill cohorts; Phase 1b dose escalation: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy. * Phase 1a dose expansion: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy. * Eastern Cooperative Oncology Group performance status 0 or 1. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. * Adequate organ function. * Individuals of childbearing potential who engage in heterosexual intercourse must agree to use method(s) of contraception. * Tissue requirements: * Phase 1a dose escalation, Phase 1a dose expansion, and Phase 1b dose escalation: Must provide pre-treatment adequate tumor tissue sample prior to enrolment. * Phase 1a backfill cohorts: Individuals must have fresh pre-treatment and on-treatment biopsy for biomarker analysis. * Life expectancy ≥ 3 months. Key
Exclusion criteria
* Positive serum pregnancy test or lactating female. * Prohibited concurrent anticancer therapy listed in the protocol. * Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: major surgery (\<28 days), immunotherapy or biologic therapy (\< 28 days), chemotherapy (\< 21 days), targeted small molecule therapy (\< 14 days or \< 5 half-lives whichever is shorter), hormonal therapy or other adjunctive therapy (\< 14 days) or radiotherapy (\< 21 days). * Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. * Diagnosis of immunodeficiency, either primary or acquired, or systemic steroid requirement of \> 10 mg of prednisone or equivalent. * History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy. * History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment. * Concurrent active second malignancy. Note: Individuals with a history of malignancy that have been completely treated, with no evidence of active cancer for 2 years prior to enrollment, or participants with surgically cured tumors with low risk of recurrence are allowed to enroll. * Have known active central nervous system (CNS) metastases and/ or carcinomatous meningitis. * Significant cardiovascular disease. * Have active serious infection requiring antibiotics. * Have active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). * History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis). * Symptomatic ascites or pleural effusion. * Live vaccines within 28 days of initiation of investigational product(s). Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | First dose date up to 90 days post last dose (Up to 24 months) |
| Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) | Day 1 up to 4 weeks |
| Maximum Tolerable Dose (MTD) of GS-4528 | Day 1 up to 4 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) parameter: Cmax of GS-4528 as Monotherapy and in Combination With Anti-PD-1 Monoclonal Antibody | Predose on Day 1 and post dose up to end of treatment (EOT, Up to 24 months) | Cmax is defined as the maximum observed concentration of drug. |
| PK parameter: Cmin of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody | Predose on Day 1 and post dose up to EOT (Up to 24 months) | Cmin is defined as the minimum observed concentration of drug. |
| PK parameter: AUC of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody | Predose on Day 1 and post dose up to EOT (Up to 24 months) | AUC is defined as the area under the concentration versus time curve. |
| Serum Concentrations of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody | Predose on Day 1 and post dose up to EOT (Up to 24 months) | — |
| Percentage of Participants who Develop Antidrug Antibody (ADA) Against GS-4528 | Predose on Day 1 and post dose up to 60 day follow-up (Up to 24 months) | — |
Countries
Canada, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed