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)

• ClinicalTrials.gov Identifier: NCT03337698
• Recruitment Status: Recruiting
• First Posted: November 9, 2017
• Last Update Posted: January 22, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: November 7, 2017
• First Posted Date: November 9, 2017
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: January 2, 2018
• Estimated Primary Completion Date: February 1, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 7, 2017): 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 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 13, 2020)

• Progression Free Survival (PFS) [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 3-5 years) ]
• Overall Survival After Randomization [ Time Frame: Randomization to death from any cause (up to approximately 3-5 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 3-5 years) ]
• Disease Control [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 3-5 years) ]
• Percentage of Participants with Adverse Events [ Time Frame: Baseline through the end of the study (approximately 3-5 years) ]

Original Secondary Outcome Measures (submitted: November 7, 2017)

• Progression Free Survival (PFS) [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 3-5 years) ]
• Overall Survival After Randomization [ Time Frame: Randomization to death from any cause (up to approximately 3-5 years) ]
• Duration of Response [ Time Frame: First occurrence of a documented objective response to disease progression or death (up to approximately 3-5 years) ]
• Disease Control [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 3-5 years) ]
• Percentage of Participants with Adverse Events [ Time Frame: Randomization through the end of the study (approximately 3-5 years) ]
• Plasma or Serum Concentration of Atezolizumab [ Time Frame: Day 1, Cycle 1 prior to study treatment and 30 minutes after IV; Day 1 of cycles 2,3,4,8,12 and 16, prior to study treatment; Treatment discontinuation; 120 days after last dose of Atezolizumab ]
• Plasma or Serum Concentration of Cobimetinib [ Time Frame: Day 15, Cycle 1 prior to treatment and 2-4 hours after dose ]
• Plasma or Serum Concentration of RO6958688 [ Time Frame: Day 1, Cycles 1-17 and subsequent, prior to treatment and at end of RO6958688 infusion; at treatment discontinuation; 30 days after last dose of atezolizumab ]
• Plasma or Serum Concentration of Docetaxel [ Time Frame: Day 1, Cycle 1 5 minutes before end of infusion and 1 hour after ]
• Plasma or Serum Concentration of BL-8040 [ Time Frame: Priming period Day 1 before treatment, 1 hour after dose and Day 5 1 hour after dose; Day 15, Cycle 1, and Day 1, Cycles 2, 3, 4, 8, 12, 16 before treatment, 1 hour after dose; Day 1, Cycle 20 and every 4 cycles thereafter before treatment; treatment end ]
• Plasma or Serum Concentration of Tazemetostat [ Time Frame: Day 1, Cycle 2 prior to treatment and 1,2 and 4 hours after dose; Day 1, Cycles 3 and 4 prior to treatment ]
• Plasma or Serum Concentration of CPI-444 [ Time Frame: Day 1, Cycles 2 and 4 prior to treatment and 2-5 hours after dose ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
• 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)

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• 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.
• 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: Docetaxel
  Docetaxel is administered by IV on Day 1 of each 21 day cycle. When combined with idasanutlin, docetaxel is administered by IV 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.
• 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.
• 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
• Drug: Linagliptin
  Linagliptin is administered orally once daily on Days 1 to 21 out of a 21 day cycle
• Drug: Tocilizumab
  Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms.
• Drug: Ipatasertib
  Ipatasertib will be administered orally once a day on Days 1-21 of each 28-day cycle.
• Drug: Bevacizumab
  Bevacizumab is administered by IV on Day 1 of each 21-day cycle.
• Drug: Sacituzumab Govitecan
  Sacituzumab Govitecan is administered by IV on Day 1 and 8 of each 21-day cycle.
• Other: Radiation
  Radiotherapy up to 21 days

Study Arms

• 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.

  Intervention: Drug: Atezolizumab
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: Cobimetinib
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: RO6958688
  • Drug: Tocilizumab
• 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.

  Intervention: Drug: Docetaxel
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: Cobimetinib
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: CPI-444
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: RO6958688
  • Drug: Tocilizumab
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: Ipatasertib
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: Docetaxel
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: Bevacizumab
• 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Pemetrexed
  • Drug: Carboplatin
• 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Carboplatin
  • Drug: Gemcitabine
• 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: RO6958688
  • Drug: Tocilizumab
• 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: Docetaxel
• 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Linagliptin
• 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Sacituzumab Govitecan
• 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Bevacizumab
  • Other: Radiation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 31, 2020): 380
• Original Estimated Enrollment (submitted: November 7, 2017): 307
• Estimated Study Completion Date: April 16, 2022
• Estimated Primary Completion Date: February 1, 2022 (Final data collection date for primary outcome measure)

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
• Current treatment with anti-viral therapy for hepatitis B virus (HBV)
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: BO39610 www.roche.com/about_roche/roche_worldwide.htm; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, France, Israel, Korea, Republic of, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03337698
• Other Study ID Numbers: BO39610; 2017-001267-21 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: January 2021