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Trial record 13 of 15 for:    Idasanutlin

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 : March 17, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.


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: Idasanutlin Drug: Bevacizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 305 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 : February 1, 2022
Estimated Study Completion Date : April 16, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Stage 1: Cohort 1: Atezolizumab

Patients 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.

Experimental: Stage 1: Cohort 1: Atezolizumab + Cobimetinib

Patients 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.

Experimental: Stage 1: Cohort 1: Atezolizumab + RO6958688

Patients 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.

Active Comparator: Stage 1: Cohort 2: Docetaxel

Patients 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. When combined with idasanutlin, docetaxel is administered by IV on Days 1 and 15 of each 28 day cycle.

Experimental: Stage 1: Cohort 2: Atezolizumab + Cobimetinib

Patients 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.

Experimental: Stage 1: Cohort 2: Atezolizumab + CPI-444

Patients 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.

Experimental: Stage 1: Cohort 2: Atezolizumab + RO6958688

Patients 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.

Experimental: Stage 1: Cohort 2: Atezolizumab + Ipatasertib

Patients 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.

Experimental: Stage 1: Cohort 2: Idasanutlin + Docetaxel

Patients in the Idasanutlin + Docetaxel 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 + 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. When combined with idasanutlin, docetaxel is administered by IV on Days 1 and 15 of each 28 day cycle.

Drug: Idasanutlin
Idasanutlin will be administered orally once a day on Days 1-5 of each 28 day cycle.

Experimental: Stage 1: Cohort 2: Atezolizumab + Docetaxel

Patients 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. When combined with idasanutlin, docetaxel is administered by IV on Days 1 and 15 of each 28 day cycle.

Experimental: Stage 1: Cohort 2: Atezolizumab + Bevacizumab

Patients 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.

Experimental: Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Patients in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
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.

Experimental: Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Patients in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
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

Experimental: Stage 2: Cohort 2: Atezolizumab + RO6958688
Patients in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
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.

Experimental: Stage 2: Cohort 2: Atezolizumab + Docetaxel

Patients 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. When combined with idasanutlin, docetaxel is administered by IV on Days 1 and 15 of each 28 day cycle.

Experimental: Stage 2: Cohort 2: Atezolizumab + Linagliptin
Patients in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.
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




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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) ]
  2. Overall Survival After Randomization [ Time Frame: Randomization to death from any cause (up to approximately 3-5 years) ]
  3. Percentage of Participants Who Are Alive at Month 6 and at Month 12 [ Time Frame: Month 6, Month 12 ]
  4. Duration of Response [ Time Frame: First occurrence of a documented objective response to disease progression or death (up to approximately 3-5 years) ]
  5. Disease Control [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 3-5 years) ]
  6. Percentage of Participants with Adverse Events [ Time Frame: Baseline through the end of the study (approximately 3-5 years) ]


Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
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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

Locations
Show Show 21 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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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 17, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
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
Enzyme Inhibitors