A Phase II, Randomized, Blinded, Placebo-Controlled Study of Tiragolumab, An Anti-TIGIT Antibody, In Combination With Atezolizumab In Chemotherapy-Naïve Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 135
- 试验地点
- 77
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This study will evaluate the safety and efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in chemotherapy-naive patients with locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC), excluding patients with a sensitizing EGFR mutation or ALK translocation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •ECOG Performance Status of 0 or 1
- •Histologically or cytologically documented locally advanced unresectable NSCLC, recurrent, or metastatic NSCLC of either squamous or non-squamous histology
- •No prior systemic treatment for locally advanced unresectable or metastatic NSCLC
- •Tumor PD-L1 expression
- •Measurable disease, as defined by RECIST v1.1
- •Life expectancy >=12 weeks
- •Adequate hematologic and end-organ function
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
排除标准
- •Cancer-Specific Exclusions:
- •Patients with NSCLC known to have a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Spinal cord compression not definitively treated with surgery and/or radiation, and/or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks prior to screening
- •History of leptomeningeal disease
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Uncontrolled tumor-related pain
- •Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- •Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome
- •General Medical Exclusions:
- •Pregnant and lactating women
- •Significant cardiovascular disease
- •Severe infections within 4 weeks prior to randomization
- •Major surgical procedure other than for diagnosis within 4 weeks prior to randomization
- •Treatment-Specific Exclusions:
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- •History of autoimmune disease
- •Prior allogeneic bone marrow transplantation or solid organ transplantation
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- •Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or active tuberculosis
- •Administration of a live, attenuated vaccine within 4 weeks prior to randomization
研究组 & 干预措施
Placebo + Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.
干预措施: Atezolizumab (Drug)
Placebo + Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.
干预措施: Placebo (Drug)
Tiragolumab + Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
干预措施: Tiragolumab (Drug)
Tiragolumab + Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)
PFS, defined as the time from randomization to the first occurrence of disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).
Objective Response Rate (ORR)
时间窗: From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months)
ORR, defined as a complete response (CR) or partial response (PR) on two consecutive occasions \>/=4 weeks apart, as determined by the investigator according to RECIST v1.1. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Objective Response Rate (ORR)
时间窗: From baseline until a total of 80 progression-free survival (PFS) events have occurred (up to approximately 11 months)
ORR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.
Progression-free Survival (PFS)
时间窗: From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)
PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm. Kaplan-Meier (KM) methodology was used to estimate the median PFS.
次要结局
- Percentage of Participants With Adverse Events(Up to 6 years)
- Duration of Objective Response (DOR)(Up to 6 years)
- Serum Concentrations of Tiragolumab(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days))
- Serum Concentrations of Atezolizumab(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days))
- Overall Survival (OS)(Up to 6 years)
- Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days))
- Duration of Objective Response (DOR)(Up to approximately 36 months)
- Overall Survival (OS)(Up to approximately 36 months)
- Number of Participants With Adverse Events (AEs)(From initiation of study drug up to approximately 83.7 months)
- Minimum Serum Concentration (Cmin) of Tiragolumab(Predose on Day 1 of Cycles 1, 3 and 11 (Cycle length = 21 days))
- Cmin of Atezolizumab(Predose on Day 1 of Cycles 1, 3 and 11 (Cycle length = 21 days))
- Number of Participants With Treatment-Emergent Anti-drug Antibodies (ADAs) to Tiragolumab(Up to approximately 36 months)
- Number of Participants With Treatment-Emergent ADAs to Atezolizumab(Up to approximately 36 months)