A Phase 1 Study to Evaluate the Safety and Tolerability of GS-9911 as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 45
- 试验地点
- 11
- 主要终点
- Percentage of Participants With Treatment-emergent 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-9911 when given alone or in combination with an anti-programmed cell death protein 1 (PD-1) monoclonal antibody in participants with advanced solid tumors.
The primary objectives of this study are to:
- Assess the safety and tolerability of GS-9911 as monotherapy and in combination with an anti-PD-1 monoclonal antibody in participants with advanced solid tumors
- Identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and the recommended dose for expansion (RDE) of GS-9911 as monotherapy and in combination with an anti-PD-1 monoclonal antibody 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
- •Parts A, C, and D:
- •Participants with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or are ineligible for all treatments known to confer clinical benefit
- •Participants whose cancer previously derived clinical benefit from immune checkpoint inhibitors, or who have advanced solid tumor types for which immune checkpoint inhibitors are considered the standard of care and who have received, been intolerant to, or are ineligible for all treatments known to confer clinical benefit
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Evaluable (Part A) or measurable (Parts B, C, and D) disease as per Response Criteria Evaluation in Solid Tumors (RECIST) v1.1 criteria
- •Adequate organ functions
- •Tissue requirement:
- •Parts A-D: must be willing to provide baseline tumor tissue prior to enrollment
- •Part A backfill cohorts: a biopsy should be obtained prior to treatment and on treatment, if safely feasible
- •Participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception
排除标准
- •Positive serum pregnancy test or lactating female
- •History of intolerance, hypersensitivity, or treatment discontinuation due to life- threatening immune-related adverse events on prior immunotherapy
- •Receipt of the therapies listed below within the specified timeframe prior to planned Cycle 1 Day 1 including: major surgery (< 4 weeks), immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (<14 days or 5 half-lives, whichever is sooner), hormonal or other adjunctive therapy (< 14 days), radiation therapy (< 21 days), live vaccine (< 28 days)
- •Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation
- •Diagnosis of immunodeficiency, or requires systemic corticosteroids (> 10 mg of prednisone daily, or equivalent)
- •History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study drug
- •History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, drug-induced pneumonitis, or severe radiation pneumonitis (excluding localized radiation pneumonitis)
- •Active second malignancy. Note: individuals with a history of malignancy that have been completed treated, with no evidence of active cancer for 2 years prior to enrollment, or individuals with surgically cured tumors with low risk of recurrence are allowed to enroll.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Symptomatic cardiovascular disease
- •Active serious infection requiring ongoing treatment
- •Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV.
- •Symptomatic ascites or pleural effusion
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part C: Dose Escalation: GS-9911 + Anti-PD-1 Monoclonal Antibody
Participants will receive escalating doses of GS-9911 in combination with an anti-PD-1 monoclonal antibody (zimberelimab).
干预措施: Zimberelimab (Drug)
Part D: Dose Expansion: GS-9911 + Anti-PD-1 Monoclonal Antibody
Participants will receive GS-9911 at RDE determined in Part C in combination with an anti-PD-1 monoclonal antibody (zimberelimab).
干预措施: Zimberelimab (Drug)
Part B: GS-9911 Monotherapy Dose Expansion
Participants will receive GS-9911 monotherapy at the recommended dose for expansion (RDE) determined in Part A.
干预措施: GS-9911 (Drug)
Part A: GS-9911 Monotherapy Dose Escalation
Participants will receive escalating doses of GS-9911 monotherapy.
干预措施: GS-9911 (Drug)
Part C: Dose Escalation: GS-9911 + Anti-PD-1 Monoclonal Antibody
Participants will receive escalating doses of GS-9911 in combination with an anti-PD-1 monoclonal antibody (zimberelimab).
干预措施: GS-9911 (Drug)
Part D: Dose Expansion: GS-9911 + Anti-PD-1 Monoclonal Antibody
Participants will receive GS-9911 at RDE determined in Part C in combination with an anti-PD-1 monoclonal antibody (zimberelimab).
干预措施: GS-9911 (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-emergent Adverse Events
时间窗: First dose date up to 90 days post last dose (up to 105 weeks)
Percentage of Participants With Treatment-emergent Serious Adverse Events
时间窗: First dose date up to 90 days post last dose (up to 105 weeks)
Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs) in Dose-escalation Cohorts
时间窗: First dose date up to 3 weeks
次要结局
- Plasma Concentration of GS-9911(Predose up to end of treatment (up to 105 weeks))
- Pharmacokinetic (PK) Parameter: Cmax of GS-9911(Predose up to end of treatment (up to 105 weeks))
- PK Parameter: Tmax of GS-9911(Predose up to end of treatment (up to 105 weeks))
- Area Under the Concentration-Time Curve (AUC) of GS-9911(Predose up to end of treatment (up to 105 weeks))