A Phase 1 Study to Evaluate the Safety and Tolerability of GS-2121 as Monotherapy and in Combination in Adults With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 154
- 试验地点
- 12
- 主要终点
- Parts A and B: Percentage of Participants with Adverse Events and Serious Adverse Events
研究概览
简要总结
The main goal of this first-in-human (FIH) study is to learn about the safety and dosing of GS-2121 when given alone or in combination with zimberelimab (ZIM) in participants with advanced solid tumors.
The primary objectives of this study are:
- To assess the safety and tolerability of GS-2121 as monotherapy and GS-2121 in combination with zimberelimab 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-2121 as monotherapy and in combination with zimberelimab in participants with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants diagnosed with histologically or cytologically confirmed advanced solid tumors who have progressed despite standard therapy, are intolerant to standard therapy, or are ineligible for standard therapy.
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •Tissue requirements:
- •Parts A-D: Pre-treatment tumor tissue is required.
- •Parts A and C backfill cohorts: Participants must agree to fresh pre- and on-treatment biopsies.
- •Adequate organ function.
排除标准
- •Positive serum pregnancy test or participant who is breastfeeding.
- •Requirement for ongoing therapy with any prohibited medications.
- •Any anti-cancer therapy, whether investigational or approved within protocol specified time prior to initiation of study including: major surgery (<4 weeks), experimental therapy (<21 days or <5 half-lives whichever is shorter), approved immunotherapy or biologic therapy (<28 days), approved chemotherapy (<21 days or <42 days for mitomycin or nitrosoureas), approved targeted small molecule therapy (<14 days or <5 half-lives whichever is longer), hormonal therapy or other adjunctive therapy for cancers other than cancer under evaluation in this study (<14 days) or radiation therapy (<21 days).
- •Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation.
- •Have not recovered (ie, returned to Grade 1 or baseline) from AEs due to a previously administered agent.
- •Have known active central nervous system (CNS) metastases and/or leptomeningeal disease (LMD).
- •Diagnosis of immunodeficiency, either primary or acquired.
- •History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment.
- •Have an active second malignancy.
- •Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires systemic antibiotics, antifungals, or antivirals, respectively.
- •History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
- •Ascites or pleural effusion that is symptomatic and/or requiring medical intervention.
- •Have active hepatitis B virus (HBV) or hepatitis C virus (HCV), or HIV.
- •Meet any of the following criteria for cardiac disease: Myocardial infarction or unstable angina pectoris within 6 months of enrollment. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication). Mean QT interval corrected for heart rate using the Fridericia's formula (QTcF) ≥ 470 msec. New York Heart Association Class > III congestive heart failure or known left ventricular ejection fraction < 40%.
- •Live vaccines within 28 days of initiation of study drug(s).
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part B: GS-2121 Monotherapy Dose Expansion
Participants with selected indications will receive GS-2121 monotherapy at the recommended dose for expansion.
干预措施: GS-2121 (Drug)
Part A: GS-2121 Monotherapy Dose Escalation
Participants will receive escalating doses of GS-2121 monotherapy until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol.
干预措施: GS-2121 (Drug)
Part C: Combination Dose Escalation of GS-2121 with Zimberelimab
Participants will receive escalating doses of GS-2121 in combination with zimberelimab until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol.
干预措施: GS-2121 (Drug)
Part D: Combination Dose Expansion of GS-2121 with Zimberelimab
Participants with selected indications will receive GS-2121 at the recommended dose for expansion in combination with zimberelimab.
干预措施: GS-2121 (Drug)
Part C: Combination Dose Escalation of GS-2121 with Zimberelimab
Participants will receive escalating doses of GS-2121 in combination with zimberelimab until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol.
干预措施: Zimberelimab (Drug)
Part D: Combination Dose Expansion of GS-2121 with Zimberelimab
Participants with selected indications will receive GS-2121 at the recommended dose for expansion in combination with zimberelimab.
干预措施: Zimberelimab (Drug)
结局指标
主要结局
Parts A and B: Percentage of Participants with Adverse Events and Serious Adverse Events
时间窗: First dose up to 90 days post last dose (up to approximately 118 weeks)
Parts A and B: Percentage of Participants with Laboratory Abnormalities
时间窗: First dose up to 90 days post last dose (up to approximately 118 weeks)
Part A: Percentage of Participants with Dose-Limiting Toxicities (DLTs) During Dose Escalation
时间窗: Day 1 up to Day 21
DLTs are defined as any of the protocol-specified treatment-emergent adverse events (AEs) with onset within the DLT-evaluation period for the corresponding dose.
Parts C and D: Percentage of Participants with Adverse Events and Serious Adverse Events
时间窗: First dose up to 90 days post last dose (up to approximately 118 weeks)
Parts C and D: Percentage of Participants with Laboratory Abnormalities
时间窗: First dose up to 90 days post last dose (up to approximately 118 weeks)
Part C: Percentage of Participants with DLTs During Dose Escalation
时间窗: Day 1 up to Day 21
DLTs are defined as any of the protocol-specified treatment-emergent adverse events (AEs) with onset within the DLT-evaluation period for the corresponding dose.
次要结局
- Parts A and B: Plasma Concentration of GS-2121 and Active Metabolite(Predose and postdose up to end of treatment (up to 105 weeks))
- Parts A and B: PK Parameter: AUC0-24 of GS-2121(Predose and postdose up to end of treatment (up to 105 weeks))
- Parts A and B: PK Parameter: Tmax of GS-2121(Predose and postdose up to end of treatment (up to 105 weeks))
- Parts A and B: PK Parameter: Cmax of GS-2121(Predose and postdose up to end of treatment (up to 105 weeks))
- Parts C and D: Plasma Concentration of GS-2121 and Active Metabolite(Predose and postdose up to end of treatment (up to 105 weeks))
- Parts C and D: PK Parameter: AUC0-24 of GS-2121(Predose and postdose up to end of treatment (up to 105 weeks))
- Parts C and D: PK Parameter: Cmax of GS-2121(Predose and postdose up to end of treatment (up to 105 weeks))
- Parts C and D: PK Parameter: Tmax of GS-2121(Predose and postdose up to end of treatment (up to 105 weeks))