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)
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 314
- Locations
- 29
- Primary Endpoint
- Percentage of Participants with Objective Response
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Atezolizumab
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.
Intervention: Atezolizumab
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.
Intervention: Cobimetinib
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.
Intervention: Atezolizumab
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.
Intervention: RO6958688
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.
Intervention: Tocilizumab
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.
Intervention: Docetaxel
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.
Intervention: Atezolizumab
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.
Intervention: Cobimetinib
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.
Intervention: Atezolizumab
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.
Intervention: CPI-444
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.
Intervention: Atezolizumab
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.
Intervention: RO6958688
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.
Intervention: Tocilizumab
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.
Intervention: Atezolizumab
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.
Intervention: Ipatasertib
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.
Intervention: Atezolizumab
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.
Intervention: Docetaxel
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.
Intervention: Atezolizumab
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.
Intervention: Bevacizumab
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.
Intervention: Atezolizumab
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.
Intervention: Pemetrexed
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.
Intervention: Carboplatin
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.
Intervention: Atezolizumab
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.
Intervention: Carboplatin
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.
Intervention: Gemcitabine
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.
Intervention: Atezolizumab
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.
Intervention: RO6958688
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.
Intervention: Tocilizumab
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.
Intervention: Atezolizumab
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.
Intervention: Docetaxel
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.
Intervention: Atezolizumab
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.
Intervention: Linagliptin
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.
Intervention: Atezolizumab
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.
Intervention: Sacituzumab Govitecan
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.
Intervention: Atezolizumab
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.
Intervention: Bevacizumab
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.
Intervention: Radiation
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.
Intervention: Atezolizumab
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.
Intervention: Evolocumab
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.
Intervention: Atezolizumab
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.
Intervention: Tiragolumab
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.
Intervention: Atezolizumab
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.
Intervention: Tiragolumab
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.
Intervention: XL092
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.
Intervention: Atezolizumab
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.
Intervention: Camonsertib
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.
Intervention: Atezolizumab
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.
Intervention: Bevacizumab
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.
Intervention: Camonsertib
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.
Intervention: Atezolizumab
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.
Intervention: Bevacizumab
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.
Intervention: Tiragolumab
Outcomes
Primary Outcomes
Percentage of Participants with Objective Response
Time Frame: Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter
Secondary Outcomes
- 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))