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)
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| ClinicalTrials.gov Identifier: NCT03337698 |
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Recruitment Status :
Recruiting
First Posted : November 9, 2017
Last Update Posted : March 6, 2023
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This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in patients with metastatic non-small cell lung cancer (NSCLC).
Two cohorts will be enrolled in parallel in this study: the first-line (1L) cohort will consist of patients who have not received any systemic therapy for their disease and the second-line (2L) cohort will consist of patients who progressed during or after receiving a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor treatment. In each cohort, eligible patients will be assigned to one of several treatment arms.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Carcinoma, Non-Small-Cell Lung | Drug: Atezolizumab Drug: Cobimetinib Drug: RO6958688 Drug: Docetaxel Drug: CPI-444 Drug: Pemetrexed Drug: Carboplatin Drug: Gemcitabine Drug: Linagliptin Drug: Tocilizumab Drug: Ipatasertib Drug: Bevacizumab Drug: Sacituzumab Govitecan Other: Radiation Drug: Evolocumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 435 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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) |
| Actual Study Start Date : | January 2, 2018 |
| Estimated Primary Completion Date : | April 12, 2024 |
| Estimated Study Completion Date : | August 1, 2025 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Cobimetinib Cobimetinib is administered orally on Days 1-21 of a 28 day cycle. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: RO6958688 Cycle 1: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle at increasing dosage. Subsequent cycles: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle. Drug: Tocilizumab Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms. |
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Active Comparator: 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. |
Drug: Docetaxel
Docetaxel is administered by IV on Day 1 of each 21 day cycle. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Cobimetinib Cobimetinib is administered orally on Days 1-21 of a 28 day cycle. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: CPI-444 CPI-444 is administered orally twice daily on Days 1- 21, of a 21 day cycle. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: RO6958688 Cycle 1: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle at increasing dosage. Subsequent cycles: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle. Drug: Tocilizumab Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Ipatasertib Ipatasertib will be administered orally once a day on Days 1-21 of each 28-day cycle. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Docetaxel Docetaxel is administered by IV on Day 1 of each 21 day cycle. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Bevacizumab Bevacizumab is administered by IV on Day 1 of each 21-day cycle. |
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Experimental: 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.
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Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Pemetrexed Pemetrexed is administered by IV on Day 1 of a 21 day cycle. Drug: Carboplatin Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day cycle. |
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Experimental: 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.
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Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Carboplatin Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day cycle. Drug: Gemcitabine Gemcitabine is administered by IV on Days 1 and 8 of the first 4 or 6 cycles out of a 21 day cycle. |
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Experimental: 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.
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Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: RO6958688 Cycle 1: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle at increasing dosage. Subsequent cycles: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle. Drug: Tocilizumab Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms. |
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Experimental: 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. |
Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Docetaxel Docetaxel is administered by IV on Day 1 of each 21 day cycle. |
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Experimental: 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.
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Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Linagliptin Linagliptin is administered orally once daily on Days 1 to 21 out of a 21 day cycle. |
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Experimental: 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.
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Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Sacituzumab Govitecan Sacituzumab Govitecan is administered by IV on Day 1 and 8 of each 21-day cycle. |
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Experimental: 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.
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Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Bevacizumab Bevacizumab is administered by IV on Day 1 of each 21-day cycle. Other: Radiation Radiotherapy up to 21 days |
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Experimental: 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.
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Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle. Drug: Evolocumab Evolocumab is administered subcutaneously at a dose of 140 mg on Days 1 and 15 of each 28-day cycle. |
- 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 ]
- Progression Free Survival (PFS) [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 7 years) ]
- Overall Survival After Randomization [ Time Frame: Randomization to death from any cause (up to approximately 7 years) ]
- Percentage of Participants Who Are Alive at Month 6 and at Month 12 [ Time Frame: Month 6, Month 12 ]
- Duration of Response [ Time Frame: First occurrence of a documented objective response to disease progression or death (up to approximately 7 years) ]
- Disease Control [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 7 years) ]
- Percentage of Participants with Adverse Events [ Time Frame: Baseline through the end of the study (approximately 7 years) ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03337698
| Contact: Reference Study ID Number: BO39610 https://forpatients.roche.com/ | 888-662-6728 (U.S. and Canada) | global-roche-genentech-trials@gene.com |
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| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT03337698 |
| Other Study ID Numbers: |
BO39610 2017-001267-21 ( EudraCT Number ) |
| First Posted: | November 9, 2017 Key Record Dates |
| Last Update Posted: | March 6, 2023 |
| Last Verified: | March 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Carcinoma, Non-Small-Cell Lung Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Linagliptin Gemcitabine Bevacizumab Carboplatin Docetaxel |
Pemetrexed Atezolizumab Evolocumab Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents |