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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: Docetaxel
CPI-444Stage 1: Cohort 2: Atezolizumab + CPI-444
PemetrexedStage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
CarboplatinStage 2: Cohort 1: Atezolizumab + Pemetrexed + 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
IdasanutlinStage 1: Cohort 2: Idasanutlin + Docetaxel

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 ComparatorPatients in the Atezolizumab arm will receive treatment 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 + CobimetinibExperimentalPatients in the Atezolizumab + Cobimetinib arm will receive treatment 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 + RO6958688ExperimentalPatients in the Atezolizumab + RO6958688 arm will receive treatment 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 ComparatorPatients in the Docetaxel arm will receive treatment 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 + CobimetinibExperimentalPatients in the Atezolizumab + Cobimetinib arm will receive treatment 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-444ExperimentalPatients in the Atezolizumab + CPI-444 arm will receive treatment 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 + RO6958688ExperimentalPatients in the Atezolizumab + RO6958688 arm will receive treatment 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 + IpatasertibExperimentalPatients in the Atezolizumab + Ipatasertib arm will receive treatment until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
  • Atezolizumab
  • Ipatasertib
Stage 1: Cohort 2: Idasanutlin + DocetaxelExperimentalPatients in the Idasanutlin + Docetaxel arm will receive treatment until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + RO6958688 or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.
  • Docetaxel
  • Idasanutlin
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + CarboplatinExperimentalPatients in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Pemetrexed
  • Carboplatin
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + CarboplatinExperimentalPatients in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Carboplatin
  • Gemcitabine
Stage 2: Cohort 2: Atezolizumab + RO6958688ExperimentalPatients in the Atezolizumab + RO6958688 arm will receive treatment until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • RO6958688
  • Tocilizumab
Stage 2: Cohort 2: Atezolizumab + DocetaxelExperimentalPatients in the Atezolizumab + Docetaxel arm will receive treatment until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Docetaxel
Stage 2: Cohort 2: Atezolizumab + LinagliptinExperimentalPatients in the Atezolizumab + Linagliptin arm will receive treatment until unacceptable toxicity or loss of clinical benefit.
  • Atezolizumab
  • Linagliptin

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 DNA (ctDNA) testing (only if an idasanutlincontaining arm is open for
             enrollment)

          -  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:
Measure: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
Safety Issue:
Description:
Measure:Plasma Concentration of Cobimetinib
Time Frame:Day 15, Cycle 1: prior to treatment and 2-4 hours after dose
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Plasma Concentration of Docetaxel
Time Frame:Arm with idasanutlin: Day 1, Cycle 1: pre-dose, 30-60 min after infusion; pre-dose Day 1 of Cycles 2, 4, 6, 8 and every 4th cycle thereafter. Arm with atezolizumab: Day 1, Cycle 1: 5 min before end of docetaxel infusion, 1 hour after docetaxel infusion
Safety Issue:
Description:
Measure:Plasma Concentration of Ipatasertib
Time Frame:Day 15, Cycle 1: prior to treatment and 1-3 hours after dose
Safety Issue:
Description:
Measure:Plasma Concentration of Idasanutlin
Time Frame:Day 1, Cycle 1: prior to treatment and 2 and 6 hours after dose; Day 8, Cycle 1 (72 hours after Day 5 dose); Day 1 of Cycles 2, 4, 6, 8 and every 4th cycle thereafter: 4-6 hours after dose; at treatment discontinuation
Safety Issue:
Description:
Measure:Plasma Concentration of CPI-444
Time Frame:Day 1, Cycles 2 and 4: prior to treatment and 2-5 hours after dose
Safety Issue:
Description:
Measure:Plasma Concentration of Linagliptin
Time Frame:Day 1, Cycle 1: 2 hours post-dose; Day 1 of Cycles 2 and 3: pre-treatment.
Safety Issue:
Description:

Details

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

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