A Phase Ib, Open-Label Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 25
- 主要终点
- Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of GDC-1971 when administered in combination with atezolizumab in participants with locally advanced or metastatic solid tumors.
The study will have 2 stages- dose finding stage and expansion stage. In expansion stage participants with non-small cell lung cancer programmed death ligand -1 high (NSCLC PD L-1 high), NSCLC PD L-1 low, head and neck squamous cell carcinoma (HNSCC) PD L-1 positive, BRAF wild type (BRAF WT) melanoma and any locally advanced or metastatic solid tumors will be enrolled.
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
- •Has Eastern Cooperative Oncology Group(ECOG) Performance Status of 0 or 1
- •Has Life expectancy >= 12 weeks
- •Adequate organ function
- •Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
- •Inclusion Criteria for Dose-Finding Stage:
- •Histologically confirmed locally advanced or metastatic solid tumor that has progressed after at least one available standard therapy or for which approved standard therapy has proven to be ineffective or intolerable
- •Inclusion Criteria for Expansion Stage: NSCLC Cohort
- •Histologically confirmed locally advanced or metastatic NSCLC
- •Absence of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)
- •PD- L1 positive
- •No prior systemic therapy for locally advanced or metastatic NSCLC
- •Inclusion Criteria for Expansion Stage: HNSCC Cohort
- •Histologically confirmed recurrent, or metastatic HNSCC
- •PD-L1 positive
- •No prior systemic therapy for recurrent or metastatic HNSCC
- •Inclusion Criteria for Expansion Stage: BRAF WT melanoma Cohort
- •Histologically confirmed locally advanced or metastatic or unresectable locally advanced cutaneous BRAF WT melanoma or melanomas of unknown primary that are non-mucosal and non -uveal that has progressed on or after treatment that included anti PD1 or anti PD-L1 therapy
- •Inclusion Criteria for Expansion Stage: Other Advanced or Metastatic Solid Tumors Cohort
- •Histologically confirmed locally advanced or metastatic solid tumor that has progressed after at least one available standard therapy or for which approved standard therapy has proven to be ineffective or intolerable, standard therapy is considered inappropriate, or an investigational agent is a recognized standard of care
排除标准
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
- •Has leptomeningeal disease or carcinomatous meningitis
- •Has uncontrolled hypertension
- •Has left ventricular ejection fraction < institutional lower limit of normal or < 50%
- •Has clinically significant history of liver disease including viral or other hepatitis, current alcohol abuse, or cirrhosis
- •Has an active or history of autoimmune disease or immune deficiency including myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or multiple sclerosis. Participants with a history of autoimmune- related hypothyroidism on thyroid replacement hormone or with controlled Type I diabetes mellitus on a stable dose of an insulin regimen are eligible for this study
研究组 & 干预措施
Dose-finding Stage: GDC-1971
Participants will receive GDC-1971 tablet or capsule at assigned dose, orally once daily (QD) on Days 1-21 of each cycle, along with atezolizumab 1200 milligrams (mg) intravenous (IV) infusion once every 3 weeks (Q3W), until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet versus (vs) capsule formulations.
干预措施: GDC-1971 (Drug)
Dose-finding Stage: GDC-1971
Participants will receive GDC-1971 tablet or capsule at assigned dose, orally once daily (QD) on Days 1-21 of each cycle, along with atezolizumab 1200 milligrams (mg) intravenous (IV) infusion once every 3 weeks (Q3W), until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet versus (vs) capsule formulations.
干预措施: Atezolizumab (Drug)
Expansion Stage: GDC-1971
Participants will receive GDC-1971 orally at the assigned dose QD on Days 1-21 of each cycle and atezolizumab 1200 mg IV on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet vs capsule formulation, the effect of food and acid-reducing agents on GDC-1971.
干预措施: GDC-1971 (Drug)
Expansion Stage: GDC-1971
Participants will receive GDC-1971 orally at the assigned dose QD on Days 1-21 of each cycle and atezolizumab 1200 mg IV on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet vs capsule formulation, the effect of food and acid-reducing agents on GDC-1971.
干预措施: Atezolizumab (Drug)
Expansion Stage: GDC-1971
Participants will receive GDC-1971 orally at the assigned dose QD on Days 1-21 of each cycle and atezolizumab 1200 mg IV on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet vs capsule formulation, the effect of food and acid-reducing agents on GDC-1971.
干预措施: Omeprazole (Drug)
结局指标
主要结局
Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs
时间窗: Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years)
Percentage of Participants With Adverse Events (AEs)
时间窗: Up to approximately 2.5 years
Percentage of Participants With Clinically Significant Change From Baseline in RR and QT Intervals as Measured by Electrocardiogram (ECG)
时间窗: Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years)
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
时间窗: From Day 1 to Day 21 of Cycle 1 of the dose finding stage
Percentage of Participants With Clinically Significant Change from Baseline in Clinical Laboratory Test Results
时间窗: Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years)
Plasma Concentration of GDC-1971
时间窗: Up to approximately 2.5 years
次要结局
- Duration of Response (DOR)(Up to approximately 2.5 years)
- Area Under the Concentration-Time Curve From Time 0 to 96 hours (AUC0-96 hr) Following GDC-1971 Capsule or Tablet Administration(Up to approximately 2.5 years)
- Cmax of GDC-1971 Following Capsule or Tablet Administration(Up to approximately 2.5 years)
- AUC inf Following GDC-1971 Tablet Administration Under Fasted and Fed Conditions(Up to approximately 2.5 years)
- Objective Response Rate (ORR)(Up to approximately 2.5 years)
- Progression Free Survival (PFS)(Up to approximately 2.5 years)
- AUC From Time 0 to Infinity (AUCinf) Following GDC-1971 Capsule or Tablet Administration(Up to approximately 2.5 years)
- Cmax of GDC-1971 Following Tablet Administration Under Fasted and Fed Conditions(Up to approximately 2.5 years)
- PFS Rate(Month 6)
- Overall Survival (OS) Rate(Months 6 and 12)
- AUC 0-96 hr Following GDC-1971 Tablet Administration Under Fasted and Fed Conditions(Up to approximately 2.5 years)
- AUC 0-24 hr at Steady State Following GDC-1971 Tablet Administration and in Combination With Omeprazole(Up to approximately 2.5 years)
- Cmax at Steady State Following GDC-1971 Tablet Administration and in Combination With Omeprazole(Up to approximately 2.5 years)