A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Non-Small Cell Lung Cancer (Morpheus-Lung)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 314
- 试验地点
- 58
- 主要终点
- Percentage of Participants with Objective Response
研究概览
简要总结
This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC).
Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of participants with tumor PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC, and Cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression. In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). Participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen (Stage 2).
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
- 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
- •General Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) performance Status of 0 or 1
- •Life expectancy greater than or equal to 3 months
- •Histologically or cytologically confirmed metastatic, non-squamous or squamous Non-Small Cell Lung Cancer (NSCLC)
- •Measurable disease (at least one target lesion)
- •Adequate hematologic and end-organ function
- •Tumor accessible for biopsy
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
- •Inclusion Criteria for Cohort 1
- •No prior systemic therapy for metastatic NSCLC
- •High tumor PD-L1 expression, defined as Tumor Proportion Score (TPS) or TCs >= 50% or TC3
- •Inclusion Criteria for Cohort 2
- •- Disease progression during or following treatment for metastatic or locally advanced, inoperable NSCLC
排除标准
- •Prior allogeneic stem cell or solid organ transplantation
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •History of leptomeningeal disease
- •Active or history of autoimmune disease or immune deficiency
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- •History of malignancy other than NSCLC within 2 years prior to screening
- •Active tuberculosis
- •Severe infection within 4 weeks prior to initiation of study treatment
研究组 & 干预措施
Stage 1: Cohort 2: Atezolizumab + Docetaxel
Participants in Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Ipatasertib
Participants in the Atezolizumab + Ipatasertib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Ipatasertib (Drug)
Stage 1: Cohort 2: Atezolizumab + Docetaxel
Participants in Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Docetaxel (Drug)
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Pemetrexed (Drug)
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Carboplatin (Drug)
Stage 2: Cohort 2: Atezolizumab + Docetaxel
Participants in the Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who have received treatment with Atezolizumab + Docetaxel in Stage 1 will not receive this treatment in Stage 2.
干预措施: Docetaxel (Drug)
Stage 1: Cohort 2: Atezolizumab + Camonsertib
Participants in the Atezolizumab + Camonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Camonsertib (Drug)
Stage 1: Cohort 1: Atezolizumab + Tiragolumab
Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib
Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Evolocumab
Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Evolocumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib
Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Bevacizumab (Drug)
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Carboplatin (Drug)
Stage 1: Cohort 2: Atezolizumab + Cobimetinib
Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 1: Atezolizumab + Cobimetinib
Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.
Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 2: Cohort 2: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Tocilizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy
Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Radiation (Other)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib
Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Camonsertib (Drug)
Stage 1: Cohort 1: Atezolizumab
Participants in the Atezolizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 1: Atezolizumab + Cobimetinib
Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.
Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Cobimetinib (Drug)
Stage 1: Cohort 1: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.
Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 1: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.
Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: RO6958688 (Drug)
Stage 1: Cohort 1: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.
Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Tocilizumab (Drug)
Stage 1: Cohort 2: Docetaxel
Participants in the Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or disease progression.
Participants who progressed on treatment may have the option of receiving Atezolizumab + RO6958688 or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Docetaxel (Drug)
Stage 1: Cohort 2: Atezolizumab + Cobimetinib
Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Cobimetinib (Drug)
Stage 1: Cohort 2: Atezolizumab + CPI-444
Participants in the Atezolizumab + CPI-444 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + CPI-444
Participants in the Atezolizumab + CPI-444 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: CPI-444 (Drug)
Stage 1: Cohort 2: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: RO6958688 (Drug)
Stage 1: Cohort 2: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Tocilizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Ipatasertib
Participants in the Atezolizumab + Ipatasertib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab
Participants in Atezolizumab + Bevacizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab
Participants in Atezolizumab + Bevacizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
干预措施: Bevacizumab (Drug)
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Gemcitabine (Drug)
Stage 2: Cohort 2: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 2: Cohort 2: Atezolizumab + RO6958688
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: RO6958688 (Drug)
Stage 2: Cohort 2: Atezolizumab + Docetaxel
Participants in the Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants who have received treatment with Atezolizumab + Docetaxel in Stage 1 will not receive this treatment in Stage 2.
干预措施: Atezolizumab (Drug)
Stage 2: Cohort 2: Atezolizumab + Linagliptin
Participants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 2: Cohort 2: Atezolizumab + Linagliptin
Participants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Linagliptin (Drug)
Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan
Participants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan
Participants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Sacituzumab Govitecan (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy
Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy
Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Bevacizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Evolocumab
Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 1: Atezolizumab + Tiragolumab
Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Tiragolumab (Drug)
Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)
Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)
Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Tiragolumab (Drug)
Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)
Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: XL092 (Drug)
Stage 1: Cohort 2: Atezolizumab + Camonsertib
Participants in the Atezolizumab + Camonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab
Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Atezolizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab
Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Bevacizumab (Drug)
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab
Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
干预措施: Tiragolumab (Drug)
结局指标
主要结局
Percentage of Participants with Objective Response
时间窗: Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter
次要结局
- Disease Control(Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years))
- Progression Free Survival (PFS)(Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years))
- Percentage of Participants Who Are Alive at Month 6 and at Month 12(Month 6, Month 12)
- Percentage of Participants with Adverse Events(Baseline through the end of the study (approximately 8 years))
- Overall Survival After Randomization(Randomization to death from any cause (up to approximately 8 years))
- Duration of Response(First occurrence of a documented objective response to disease progression or death (up to approximately 8 years))