A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
Phase 1
Active, not recruiting
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Other: Radiation
- Registration Number
- NCT03337698
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 314
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stage 1: Cohort 1: Atezolizumab + RO6958688 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. Stage 1: Cohort 2: Atezolizumab + CPI-444 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. Stage 2: Cohort 2: Atezolizumab + Linagliptin Atezolizumab Participants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 2: Atezolizumab + Linagliptin Linagliptin Participants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan Atezolizumab Participants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan Sacituzumab Govitecan Participants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy Bevacizumab Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy Radiation Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Evolocumab Atezolizumab Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 1: Atezolizumab + Tiragolumab Atezolizumab Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Camonsertib Camonsertib Participants in the Atezolizumab + Camonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib Camonsertib Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 2: Atezolizumab + RO6958688 RO6958688 Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + RO6958688 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. Stage 1: Cohort 1: Atezolizumab 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. Stage 1: Cohort 1: Atezolizumab + Cobimetinib Atezolizumab 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. Stage 1: Cohort 1: Atezolizumab + RO6958688 Atezolizumab 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. Stage 1: Cohort 1: Atezolizumab + Cobimetinib 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. Stage 1: Cohort 1: Atezolizumab + RO6958688 Tocilizumab 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. Stage 1: Cohort 2: Docetaxel 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. Stage 1: Cohort 2: Atezolizumab + Cobimetinib Atezolizumab 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. Stage 1: Cohort 2: Atezolizumab + Cobimetinib 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. Stage 1: Cohort 2: Atezolizumab + CPI-444 Atezolizumab 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. Stage 1: Cohort 2: Atezolizumab + RO6958688 Atezolizumab 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. Stage 1: Cohort 2: Atezolizumab + Ipatasertib 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. Stage 1: Cohort 2: Atezolizumab + Ipatasertib Atezolizumab 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. Stage 1: Cohort 2: Atezolizumab + Docetaxel 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. Stage 1: Cohort 2: Atezolizumab + Bevacizumab Atezolizumab 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. Stage 1: Cohort 2: Atezolizumab + RO6958688 Tocilizumab 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. Stage 1: Cohort 2: Atezolizumab + Docetaxel Atezolizumab 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. Stage 1: Cohort 2: Atezolizumab + Bevacizumab 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. Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin Atezolizumab Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin Pemetrexed Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin Carboplatin Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin Atezolizumab Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin Gemcitabine Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 2: Atezolizumab + RO6958688 Atezolizumab Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin Carboplatin Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 2: Atezolizumab + RO6958688 Tocilizumab Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 2: Cohort 2: Atezolizumab + Docetaxel Atezolizumab 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. Stage 2: Cohort 2: Atezolizumab + Docetaxel 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. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy Atezolizumab Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Evolocumab Evolocumab Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 1: Atezolizumab + Tiragolumab Tiragolumab Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib) Atezolizumab Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib) Tiragolumab Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Camonsertib Atezolizumab Participants in the Atezolizumab + Camonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib Atezolizumab Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib Bevacizumab Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab Bevacizumab Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab Atezolizumab Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab Tiragolumab Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib) XL092 Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Objective Response Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter
- Secondary Outcome Measures
Name Time Method 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)
Trial Locations
- Locations (32)
Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
🇺🇸Las Vegas, Nevada, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Blacktown Hospital
🇦🇺Blacktown, New South Wales, Australia
Peter Mac Callum Cancer Center
🇦🇺East Melbourne, Victoria, Australia
CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
🇫🇷Bordeaux, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Centre Léon Bérard
🇫🇷Lyon, France
Hopital de la Timone
🇫🇷Marseille, France
Institut Régional du Cancer de Montpellier
🇫🇷Montpellier, France
Institut De Cancerologie De L'Ouest
🇫🇷Saint Herblain, France
Institut Universitaire du Cancer de Toulouse-Oncopole
🇫🇷Toulouse, France
Rambam Medical Center
🇮🇱Haifa, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)
🇰🇷Songpa-gu, Korea, Republic of
ClÃnica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Fundación Jimenez DÃaz
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro-CIOCC
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
Barts Cancer Institute
🇬🇧London, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle upon Tyne, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom