A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (Morpheus Lung)
Carcinoma, Non-Small-Cell Lung
About this trial
This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung
Eligibility Criteria
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
- Availability of peripheral blood for next-generation sequencing (NGS) circulating tumor deoxyribonucleic acid (ctDNA) testing.
- 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) >= 50%
Inclusion Criteria for Cohort 2
- Disease progression during or following treatment for metastatic or locally advanced, inoperable NSCLC
Exclusion Criteria
- 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
Sites / Locations
- Smilow Cancer Hospital at Yale New Haven
- Christiana Care Health ServicesRecruiting
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
- Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749
- University Hospitals Case Medical Center; Seidman Cancer CenterRecruiting
- Cleveland Clinic
- Sarah Cannon Research Institute
- Blacktown HospitalRecruiting
- Peter Mac Callum Cancer Center
- Centre Georges Francois LeclercRecruiting
- Centre Léon Bérard
- Hopital de la TimoneRecruiting
- Institut Régional du Cancer de MontpellierRecruiting
- Institut De Cancerologie De L'Ouest; Medical OncologyRecruiting
- Institut Universitaire du Cancer de Toulouse-Oncopole; PHARMACIERecruiting
- Rambam Medical Center; OncologyRecruiting
- Rabin Medical CenterRecruiting
- Chaim Sheba Medical Center; Oncology DeptRecruiting
- Chonnam National University Hwasun Hospital
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health SystemRecruiting
- Korea University Guro HospitalRecruiting
- University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)
- Clínica Universidad de NavarraRecruiting
- Hospital Universitari Vall d'HebronRecruiting
- Hospital Universitario La PazRecruiting
- Fundación Jimenez DíazRecruiting
- Hospital Universitario HM Sanchinarro-CIOCCRecruiting
- Hospital Regional Universitario de MalagaRecruiting
- Hospital Clinico Universitario de ValenciaRecruiting
- National Cheng Kung University Hospital; Gasterointestinal
- Taipei Veterans General HospitalRecruiting
- Barts Cancer InstituteRecruiting
- The Newcastle upon Tyne Hospitals NHS Foundation TrustRecruiting
- Royal Marsden Hospital; Institute of Cancer ResearchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Arm 16
Arm 17
Arm 18
Arm 19
Arm 20
Arm 21
Active Comparator
Experimental
Experimental
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Active Comparator
Experimental
Experimental
Stage 1: Cohort 1: Atezolizumab
Stage 1: Cohort 1: Atezolizumab + Cobimetinib
Stage 1: Cohort 1: Atezolizumab + RO6958688
Stage 1: Cohort 2: Docetaxel
Stage 1: Cohort 2: Atezolizumab + Cobimetinib
Stage 1: Cohort 2: Atezolizumab + CPI-444
Stage 1: Cohort 2: Atezolizumab + RO6958688
Stage 1: Cohort 2: Atezolizumab + Ipatasertib
Stage 1: Cohort 2: Atezolizumab + Docetaxel
Stage 1: Cohort 2: Atezolizumab + Bevacizumab
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Stage 2: Cohort 2: Atezolizumab + RO6958688
Stage 2: Cohort 2: Atezolizumab + Docetaxel
Stage 2: Cohort 2: Atezolizumab + Linagliptin
Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy
Stage 1: Cohort 2: Atezolizumab + Evolocumab
Stage 1: Cohort 1: Atezolizumab + Tiragolumab
Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)
Stage 1: Cohort 2: Atezolizumab + Camonsertib
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
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.
Participants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.
Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
Participants in the Atezolizumab + Camonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.