COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03337698
Recruitment Status : Recruiting
First Posted : November 9, 2017
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE November 7, 2017
First Posted Date  ICMJE November 9, 2017
Last Update Posted Date January 22, 2021
Actual Study Start Date  ICMJE January 2, 2018
Estimated Primary Completion Date February 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 31, 2020)
380
Original Estimated Enrollment  ICMJE
 (submitted: November 7, 2017)
307
Estimated Study Completion Date  ICMJE April 16, 2022
Estimated Primary Completion Date February 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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  ICMJE Australia,   France,   Israel,   Korea, Republic of,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03337698
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP