Study of GS-4528 in Adults With Solid Tumors
- Registration Number
- NCT05840224
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 132
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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.
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Eastern Cooperative Oncology Group performance status 0 or 1.
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Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
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Adequate organ function.
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Individuals of childbearing potential who engage in heterosexual intercourse must agree to use method(s) of contraception.
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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.
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Life expectancy ≥ 3 months.
Key
- 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/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1b:Dose Escalation of GS-4528 in Combination With Anti-PD-1 Monoclonal Antibody (zimberelimab) Zimberelimab Participants will receive escalating doses of GS-4528 in combination with anti-PD1 monoclonal antibody (zimberelimab) to determine the maximum tolerated dose of GS-4528 as a combination therapy. Phase 1a: GS-4528 Monotherapy Dose Expansion GS-4528 Participants will receive GS-4528 monotherapy at the dose determined in the escalation phase. Phase 1a: GS-4528 Monotherapy Dose Escalation GS-4528 Participants will receive escalating doses of GS-4528 monotherapy to determine the maximum tolerated dose. Phase 1b:Dose Escalation of GS-4528 in Combination With Anti-PD-1 Monoclonal Antibody (zimberelimab) GS-4528 Participants will receive escalating doses of GS-4528 in combination with anti-PD1 monoclonal antibody (zimberelimab) to determine the maximum tolerated dose of GS-4528 as a combination therapy.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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) 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.
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)
Trial Locations
- Locations (16)
Chang Gung Memorial Hospital Linkuo Branch of the Chang Gung Medical Foundation
🇨🇳Taoyuan, Taiwan
The University of Washington/FHCC
🇺🇸Seattle, Washington, United States
START MADRID_Hospital Universitario Fundacion Jimenez Diaz - Unidad de Ensayos Fases I
🇪🇸Madrid, Spain
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom
University Health Network, Princess Margaret Cancer Centre
🇨🇦Toronto, Canada
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Ottawa Hospital
🇨🇦Ottawa, Canada
Severance Hospital, Yonsei University Health Systems
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Vall D'Hebron- Oncology Service
🇪🇸Barcelona, Spain
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
START MADRID_HM Sanchinarro-CIOCC-Unidad de Ensayos Fases I
🇪🇸Madrid, Spain
Clinica Universidad de Navarra- Unidad Central de Ensayos Clinicos
🇪🇸Pamplona, Spain
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
St Bartholomew's Hospital
🇬🇧London, United Kingdom
NEXT Oncology-Hospital Quironsalud Barcelona - Unidad de Ensayos Fase 1
🇪🇸Barcelona, Spain