NCT03735121已完成3 期
A Randomized, Multicenter, Phase Ib/III Study to Investigate the Pharmacokinetics, Efficacy, and Safety of Atezolizumab Subcutaneous Compared With Atezolizumab Intravenous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 438
- 试验地点
- 74
- 主要终点
- Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1
研究概览
简要总结
This study will evaluate the pharmacokinetics, safety, and efficacy of atezolizumab subcutaneous (SC) compared with atezolizumab intravenous (IV) in participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) who have not been exposed to cancer immunotherapy (CIT) and for whom prior platinum-based therapy has failed. The study is comprised of two parts, as follows: A dose-finding part (Part 1, Phase Ib) will aim to identify the dose of atezolizumab SC to be tested in Part 2. A dose-confirmation part (Part 2, Phase III, randomized) will aim to confirm that the dose moved forward from Part 1 yields drug exposure that is comparable to that of atezolizumab IV.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically or cytologically documented locally advanced or metastatic NSCLC
- •Prior platinum-containing regimen or disease recurrence ≤ 6 months since prior platinum-based adjuvant/neoadjuvant regimen.
- •Measurable disease as defined by RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Life expectancy ≥12 weeks
- •Adequate hematologic and end-organ function
- •Additional Inclusion Criteria (Part 2 Only) • Availability of tissue and known epidermal growth factor receptor (EGFR) status
排除标准
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Uncontrolled or symptomatic hypercalcemia
- •Pregnancy or breastfeeding
- •Active or history of autoimmune disease or immune deficiency
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
- •Severe infection ≤ 4 weeks
- •Treatment with therapeutic oral or IV antibiotics ≤ 2 weeks prior to study treatment
- •Significant cardiovascular disease
- •Prior allogeneic stem cell or solid organ transplantation
- •Treatment with a live, attenuated vaccine ≤ 4 weeks
- •Treatment with systemic immunostimulatory agents ≤ 4 weeks or 5 half-lives of the drug
- •Treatment with systemic immunosuppressive medication ≤ 2 weeks
- •Additional Exclusion Criteria (Part 2 Only)
- •Tested tumor programmed death-ligand-1 (PD-L1) expression status with an intention to treat the patient if positive
研究组 & 干预措施
Atezolizumab (Part 2)
Experimental
Atezolizumab
干预措施: Atezolizumab (Drug)
Cohort 1: Atezolizumab+rHuPH20 (Part 1)
Experimental
Atezolizumab+recombinant human hyaluronidase (rHuPH20), followed by Atezolizumab
干预措施: Atezolizumab (Drug)
Cohort 1: Atezolizumab+rHuPH20 (Part 1)
Experimental
Atezolizumab+recombinant human hyaluronidase (rHuPH20), followed by Atezolizumab
干预措施: rHuPH20 (Drug)
Cohort 2: Atezolizumab+rHuPH20 (Part 1)
Experimental
Atezolizumab+rHuPH20, followed by Atezolizumab
干预措施: Atezolizumab (Drug)
Cohort 2: Atezolizumab+rHuPH20 (Part 1)
Experimental
Atezolizumab+rHuPH20, followed by Atezolizumab
干预措施: rHuPH20 (Drug)
Cohort 3: Atezolizumab+rHuPH20(Part 1)
Experimental
Atezolizumab+rHuPH20, followed by Atezolizumab
干预措施: Atezolizumab (Drug)
Cohort 3: Atezolizumab+rHuPH20(Part 1)
Experimental
Atezolizumab+rHuPH20, followed by Atezolizumab
干预措施: rHuPH20 (Drug)
Atezolizumab + rHuPH20 (Part 2)
Experimental
Atezolizumab + rHuPH20
干预措施: Atezolizumab (Drug)
Atezolizumab + rHuPH20 (Part 2)
Experimental
Atezolizumab + rHuPH20
干预措施: rHuPH20 (Drug)
结局指标
主要结局
Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1
时间窗: Pre-dose on Day 1 of Cycle 2 (Cycle length=21 days for cohorts 1 and 3 and 14 days for cohort 2)
Part 2: Observed Serum Ctrough of Atezolizumab at Cycle 1
时间窗: Predose on Day 1 of Cycle 2 (Cycle length =21 days)
Part 2: Area Under the Concentration-Time Curve From Time Zero to 21 Days (AUC 0-21 d) at Cycle 1
时间窗: From start of dosing up to Day 21 in Cycle 1 (Cycle length = 21 days)
次要结局
- Part 1: Maximum Observed Serum Concentration (Cmax) of Atezolizumab(Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2))
- Part 1: Time to Maximum Serum Concentration (Tmax) of Atezolizumab(Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2))
- Part 1: Area Under the Concentration-time Curve (AUClast) of Atezolizumab(Predose and up to 21 days post dose in Cycle 1 for cohorts 1 and 3 and from predose up to 14 days post last dose in Cycle 1 for cohort 2 (Cycle length= 21 days for cohorts 1 and 3 and 14 days for cohort 2))
- Part 1: Serum Atezolizumab Concentration at Specified Timepoint During SC Administration(Cohort 1: Predose: D1 & postdose: D1, 3, 8 of C1; Cohort 2: Pre & postdose: D1 of C1, 3 & postdose: D3, 8 of C1, Predose: D1 of C2; Cohort 3: Pre & postdose: D1 of C1, 2 & postdose: D3, 8 of C1, D2, 4 & 9 of C2 & pre dose: D1 of C3)
- Part 1: Percentage of Participants With Adverse Events (AEs)(From initiation of study treatment up to approximately 69 months)
- Part 2: Percentage of Participants With AEs(From initiation of study treatment up to approximately 44.7 months)
- Part 2: Model Predicted Ctrough of Atezolizumab at Cycle 1(Cycle 1 (Cycle length=21 days))
- Part 2: Model Predicted Ctrough at Steady State (Ctrough,ss) of Atezolizumab(Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months))
- Part 2: Model Predicted AUC at Steady State (AUCss) of Atezolizumab(Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months))
- Part 2: Objective Response Rate (ORR)(Up to approximately 25 months)
- Part 2: Progression-free Survival (PFS)(Up to approximately 25 months)
- Part 2: Overall Survival (OS)(Up to approximately 44.7 months)
- Part 2: Duration of Response (DOR)(Up to approximately 25 months)
- Part 2: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL) 57 Physical Functioning Score(Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (up to approximately 44 months))
- Part 2: Change From Baseline in EORTC IL57 Role Functioning Score(Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (up to approximately 44 months))
- Part 2: Change From Baseline in EORTC IL57 Global Health Status Score(Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64 (Cycle length = 21 days), and Treatment Discontinuation Visit (up to approximately 44 months))
- Part 2: Overall Satisfaction With Treatment Over Time, Assessed by the Modified Satisfaction With Therapy (SWT) Scale of the Cancer Therapy Satisfaction Questionnaire (CTSQ)(Day 1 Cycle 3 or Treatment Discontinuation Visit (if treatment discontinued at any visit before Cycle 3) (Cycle length = 21 days))
- Part 2: Percentage of Participants by Their Responses to AE's Burden Over Time, Assessed by the Treatment-related Symptom Burden Item From the EORTC IL57(Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, and 64 (Cycle length = 21 days))
- Part 2: Percentage of Participants With Ant-Drug Antibodies (ADAs) to Atezolizumab After SC or IV Administration(From Cycle 1 Day 1 (Cycle length = 21 days) up to treatment discontinuation visit (Up to approximately 20 months))
- Part 2: Percentage of Participants With ADAs to rHuPH20 After SC Administration(From Cycle 1 Day 1 (Cycle length = 21 days) up to treatment discontinuation visit (Up to approximately 20 months))
- Part 2: Percentage of Health Care Professionals (HCPs) by Their Response to Question 2 of HCP SC Versus IV Perspective Questionnaire(After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 48 months))
- Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Versus IV Perspective Questionnaire(After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 48 months))
- Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Versus IV Perspective Questionnaire(After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 48 months))
- Part 2: Percentage of HCPs by Their Response to Question 2 of the HCP SC Perspective Questionnaire(After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 48 months))
- Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Perspective Questionnaire(After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 48 months))
- Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Perspective Questionnaire(After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 48 months))
研究者
研究点 (74)
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