Clinical Trials /

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

NCT03337698

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: BO39610
  • SECONDARY ID: 2017-001267-21
  • NCT ID: NCT03337698

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
AtezolizumabStage 1: Cohort 1: Atezolizumab
CobimetinibStage 1: Cohort 1: Atezolizumab + Cobimetinib
RO6958688Stage 1: Cohort 1: Atezolizumab + RO6958688
DocetaxelStage 1: Cohort 2: Atezolizumab + Docetaxel
CPI-444Stage 1: Cohort 2: Atezolizumab + CPI-444
PemetrexedStage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
CarboplatinStage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
GemcitabineStage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
LinagliptinStage 2: Cohort 2: Atezolizumab + Linagliptin
TocilizumabStage 1: Cohort 1: Atezolizumab + RO6958688
IpatasertibStage 1: Cohort 2: Atezolizumab + Ipatasertib
BevacizumabStage 1: Cohort 2: Atezolizumab + Bevacizumab
Sacituzumab GovitecanStage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Stage 1: Cohort 1: AtezolizumabActive ComparatorParticipants 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.
  • Atezolizumab
Stage 1: Cohort 1: Atezolizumab + CobimetinibExperimentalParticipants 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.
  • Atezolizumab
  • Cobimetinib
Stage 1: Cohort 1: Atezolizumab + RO6958688ExperimentalParticipants 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.
  • Atezolizumab
  • RO6958688
  • Tocilizumab
Stage 1: Cohort 2: DocetaxelActive ComparatorParticipants 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.
  • Docetaxel
Stage 1: Cohort 2: Atezolizumab + CobimetinibExperimentalParticipants 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.
  • Atezolizumab
  • Cobimetinib
Stage 1: Cohort 2: Atezolizumab + CPI-444ExperimentalParticipants 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.
  • Atezolizumab
  • CPI-444
Stage 1: Cohort 2: Atezolizumab + RO6958688ExperimentalParticipants 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.
  • Atezolizumab
  • RO6958688
  • Tocilizumab
Stage 1: Cohort 2: Atezolizumab + IpatasertibExperimentalParticipants 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.
  • Atezolizumab
  • Ipatasertib
Stage 1: Cohort 2: Atezolizumab + DocetaxelExperimentalParticipants 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.
  • Atezolizumab
  • Docetaxel
Stage 1: Cohort 2: Atezolizumab + BevacizumabExperimentalParticipants 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.
  • Atezolizumab
  • Bevacizumab
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + CarboplatinExperimentalParticipants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Pemetrexed
  • Carboplatin
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + CarboplatinExperimentalParticipants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Carboplatin
  • Gemcitabine
Stage 2: Cohort 2: Atezolizumab + RO6958688ExperimentalParticipants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • RO6958688
  • Tocilizumab
Stage 2: Cohort 2: Atezolizumab + DocetaxelExperimentalParticipants 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.
  • Atezolizumab
  • Docetaxel
Stage 2: Cohort 2: Atezolizumab + LinagliptinExperimentalParticipants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Linagliptin
Stage 1: Cohort 2: Atezolizumab + Sacituzumab GovitecanExperimentalParticipants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Sacituzumab Govitecan
Stage 1: Cohort 2: Atezolizumab + bevacizumab + RadiotherapyExperimentalParticipants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Bevacizumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure:Overall Survival After Randomization
Time Frame:Randomization to death from any cause (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Percentage of Participants Who Are Alive at Month 6 and at Month 12
Time Frame:Month 6, Month 12
Safety Issue:
Description:
Measure:Duration of Response
Time Frame:First occurrence of a documented objective response to disease progression or death (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Disease Control
Time Frame:Randomization to the first occurrence of disease progression or death from any cause (up to approximately 3-5 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Events
Time Frame:Baseline through the end of the study (approximately 3-5 years)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

December 3, 2020