A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Patients With Previously Untreated Advanced Non-Squamous Non-Small-Cell Lung Cancer
概览
- 阶段
- 2 期
- 干预措施
- Tiragolumab
- 疾病 / 适应症
- Non-small Cell Lung Cancer (NSCLC)
- 发起方
- Hoffmann-La Roche
- 入组人数
- 542
- 试验地点
- 242
- 主要终点
- Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2)
- 状态
- 已完成
- 最后更新
- 2个月前
概览
简要总结
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B) in participants with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC).
Eligible participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during the induction phase:
- Arm A: Tiragolumab plus atezolizumab plus pemetrexed and carboplatin or cisplatin
- Arm B: Placebo plus pembrolizumab plus pemetrexed and carboplatin or cisplatin
Following the induction phase, participants will continue maintenance therapy with either tiragolumab in combination with atezolizumab and pemetrexed (Arm A) or placebo in combination with pembrolizumab and pemetrexed (Arm B).
研究者
入排标准
入选标准
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
- •No prior systemic treatment for metastatic non-squamous NSCLC
- •Known tumor programmed death-ligand 1 (PD-L1) status
- •Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
- •Life expectancy \>= 12 weeks
- •Adequate hematologic and end-organ function
- •Negative human immunodeficiency virus (HIV) test at screening
- •Serology test negative for active hepatitis B virus or active hepatitis C virus at screening.
排除标准
- •Mutations in epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) fusion oncogene
- •Pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •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
- •History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death
- •Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
- •Treatment with investigational therapy within 28 days prior to initiation of study treatment
- •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- •Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
研究组 & 干预措施
Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Tiragolumab
Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Atezolizumab
Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Pemetrexed
Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Carboplatin
Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Cisplatin
Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Pemetrexed
Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Carboplatin
Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Cisplatin
Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Tiragolumab Matching Placebo
Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.
干预措施: Pembrolizumab
结局指标
主要结局
Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2)
时间窗: Up to approximately 5 years
Investigator-Assessed Progression-Free Survival (PFS) (Phase 2 and Phase 3)
时间窗: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years)
Overall Survival (Phase 3)
时间窗: From randomization to death from any cause (up to approximately 5 years)
次要结局
- Overall Survival (Phase 2)(From randomization to death from any cause (up to approximately 5 years))
- PFS as Determined by an Independent Review Facility (IRF) (Phase 3)(From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years))
- Investigator-assessed PFS in Participants With PD-L1 Expression at TC ≥50% and TC ≥1% Cut-off, as Determined by Central Testing With Ventana PD-L1 (SP263) Assay (Phase 3)(From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years))
- OS in Participants With PD-L1 Expression at TC ≥50% and TC ≥1% Cut-off, as Determined by Central Testing With Ventana PD-L1 (SP263) Assay (Phase 3)(From randomization to death from any cause (up to approximately 5 years))
- Investigator-Assessed PFS at 6 Months and 12 Months (Phase 3)(6 months, 12 months)
- OS Rate at 12 Months and 24 Months (Phase 3)(12 months, 24 months)
- Investigator-Assessed Confirmed ORR (Phase 3)(Up to approximately 5 years)
- Investigator-Assessed Duration of Response (DOR) (Phase 2 and Phase 3)(From first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years))
- Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning and Global Health Status (GHS)/Quality of Life (QoL) as Measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (Phase 2 and Phase 3)(Up to approximately 5 years)
- TTCD in Participant-Reported Lung Cancer Symptoms for Cough, Dyspnea, and Chest Pain, as Measured by EORTC QLQ-LC13 (Phase 2 and Phase 3)(Up to approximately 5 years)
- Percentage of Participants With Adverse Events (AEs) (Phase 2 and Phase 3)(Up to approximately 5 years)
- Participants' Response to Side Effects of Treatment as Assessed by EORTC IL46 (Phase 2 and Phase 3)(Up to approximately 5 years)
- Serum Concentration of Tiragolumab (Phase 2 and Phase 3)(Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to approximately 5 years))
- Serum Concentration of Atezolizumab (Phase 2 and Phase 3)(Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at TD visit (up to approximately 5 years))
- Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab (Phase 2 and Phase 3)(Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 5 years))
- Percentage of Participants With ADAs to Atezolizumab (Phase 2 and Phase 3)(Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 5 years))