A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 2 Study to Investigate the Efficacy and Safety of Atezolizumab With or Without Tiragolumab as Consolidation Therapy in Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed After Chemoradiotherapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 17
- 主要终点
- Investigator Assessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population
研究概览
简要总结
This is a multicenter, double-blind, placebo-controlled, randomized, phase II study to investigate the efficacy and safety of Atezolizumab with or without Tiragolumab as consolidation therapy in participants with limited stage small cell lung cancer who have not progressed during/after chemoradiotherapy.
详细描述
Participants can receive concurrent or sequential chemoradiotherapy (CRT) as per local standard of care, but they must be randomized within 6 weeks from completion of chemoradiotherapy. Participants should receive 4 cycles of chemotherapy and radiotherapy dose of 56-64 Gy (once daily) before randomization, and those participants who have not progressed during/after CRT will be stratified by response to CRT, radiotherapy timing, and be randomized in a 1:1 ratio to Atezolizumab+Tiragolumab arm or Atezolizumab+placebo arm.
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
- •Signed Informed Consent Form
- •ECOG performance status of 0 or 1
- •Histologically confirmed limited-stage SCLC.
- •Patients who have not progressed during/after chemoradiotherapy.
- •Concurrent or sequential chemoradiotherapy per local clinical practice must have been completed within 6 weeks prior to the first study treatment. If concurrent CRT is used, at least two cycles of chemotherapy should have been conducted during radiotherapy. If sequential radiotherapy is used, induction chemotherapy should be given 2 cycles of chemotherapy before thoracic radiotherapy.
- •Adequate hematologic and end organ function.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the final dose of atezolizumab or placebo, and 90 days after the final dose of tiragolumab or placebo, and 6 months for chemotherapy after the last dose of chemotherapy treatment, whichever is later.
- •For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm.
- •Patients must have recovered from all acute toxicities from previous therapy, excluding alopecia and toxicities related to prior therapy.
- •Patients must submit a pre-treatment tumor tissue sample.
排除标准
- •Histology mixtured or Extensive-stage SCLC (per the Veterans Administration Lung Study Group (VALG) staging system).
- •Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage procedures
- •Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease
- •Malignancies other than SCLC within 5 years prior to study treatment initiation, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
- •Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab and 90 days after the final dose of tiragolumab, and 6 months for chemotherapy after the final dose of the chemotherapy treatment.
- •Active or history of autoimmune disease or immune deficiency
- •Uncontrolled or symptomatic hypercalcemia
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
- •Positive test result for HIV
- •Patients with active hepatitis B or hepatitis C virus
- •Active tuberculosis
- •Severe infections within 4 weeks prior to study treatment initiation, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
- •Significant cardiovascular disease
- •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA4, anti-tigit, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- •Unresolved toxic effects of grade 2 or higher (CTCAE 5.0), including grade ≥ 2 pneumonitis from previous therapy
- •Active EBV infection or known or suspected chronic active EBV infection at screening.
研究组 & 干预措施
Arm A: Atezolizumab + Tiragolumab
Participants will receive atezolizumab + tiragolumab intravenously on the first day of each cycle. One cycle of therapy will be defined as 21 days. Atezolizumab and tiragolumab treatment will continue up to 17 doses unless investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or patient decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Atezolizumab (Drug)
Arm A: Atezolizumab + Tiragolumab
Participants will receive atezolizumab + tiragolumab intravenously on the first day of each cycle. One cycle of therapy will be defined as 21 days. Atezolizumab and tiragolumab treatment will continue up to 17 doses unless investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or patient decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Tiragolumab (Drug)
Arm B: Atezolizumab + Placebo
Participants will receive atezolizumab + placebo on the first day of each cycle. One cycle of therapy will be defined as 21 days. Atezolizumab and placebo treatment will continue up to 17 doses unless investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or patient decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Atezolizumab (Drug)
Arm B: Atezolizumab + Placebo
Participants will receive atezolizumab + placebo on the first day of each cycle. One cycle of therapy will be defined as 21 days. Atezolizumab and placebo treatment will continue up to 17 doses unless investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or patient decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Placebo (Other)
结局指标
主要结局
Investigator Assessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population
时间窗: Randomization up to approximately 48 months
PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1.
次要结局
- Objective Response Rate (ORR) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential)(Randomization up to approximately 48 months)
- PFS Rate at 1 Year and 2 Years in the ITT Ppulation(Baseline to 1 Year and 2 Years)
- Overall Survival (OS) in the ITT Population(Randomization up to approximately 48 months)
- OS Rate at 1 Year, 2 Years and 3 Years in the ITT Population(Baseline to 1 Year, 2 Years and 3 Years)
- Objective Response Rate (ORR) in the ITT Population(Randomization up to approximately 48 months)
- Duration of Response (DOR) in the ITT Population(Time from first documentation of complete response (CR) or partial response (PR) up to approximately 48 months)
- Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Response to Chemoradiotherapy (CRT) [Stable Disease (SD) vs. Complete Response (CR)/Partial Response (PR)](Randomization up to approximately 33 months)
- Overall Survival (OS) in the ITT Population by Response to CRT (SD vs. CR/PR)(Randomization up to approximately 48 months)
- Objective Response Rate (ORR) in the ITT Population by Response to CRT (SD vs. CR/PR)(Randomization up to approximately 48 months)
- Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Radiotherapy Timing (Concurrent vs. Sequential)(Randomization up to approximately 48 months)
- Overall Survival (OS) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential)(Randomization up to approximately 48 months)
- Percentage of Participants With All Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population(Baseline up to approximately 48 months)
- Percentage of Participants With Serious and Non-Serious Immune Mediated Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population(Baseline up to approximately 48 months)
- Percentage of Participants With All Adverse Events Related to Treatment in the ITT Population(Baseline up to approximately 48 months)
- Time to Deterioration (TTD) in Patient-Rported Lung Cancer Symptoms(Randomization up to approximately 48 months)
- EORTC QLQ-C30 Score(Day 1 of first 3 cycles (each cycle is 21 days) then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months)
- EORTC QLQ-LC13 Score(Day 1 of first 3 cycles (cycle length=21 days), then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months)
- EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index Based and Visual Analogue Scale (VAS) Scores(Day 1 of first 3 cycles (each cycle is 21 days) then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months)