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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) (Morpheus Lung)

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ClinicalTrials.gov Identifier: NCT03337698
Recruitment Status : Recruiting
First Posted : November 9, 2017
Last Update Posted : October 31, 2019
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 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 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 2, 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 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 Day 1 and 15 of each 28 day cycle.

Experimental: Stage 1: Cohort 1: Atezolizumab + Cobimetinib

Patients 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.

Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Day 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 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 Day 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 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 Day 1 and Day 15 of each 28 day cycle.

Experimental: Stage 1: Cohort 2: Atezolizumab + Cobimetinib

Patients 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.

Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Day 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 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 Day 1 and 15 of each 28 day cycle.

Drug: CPI-444
CPI-444 is administered orally twice daily on Days 1- 21, out of a 21 day cycle.

Experimental: Stage 1: Cohort 2: Atezolizumab + RO6958688

Patients 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.

Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Day 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 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.

Drug: Atezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Day 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 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 Day 1 and Day 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 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Patients in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment 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 Day 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 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 Day 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 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 Day 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 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 Day 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 Day 1 and Day 15 of each 28 day cycle.

Experimental: Stage 2: Cohort 2: Atezolizumab + Linagliptin
Patients in the Atezolizumab + Linagliptin arm will receive treatment 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 Day 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) ]
  7. 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 ]
  8. Plasma Concentration of Cobimetinib [ Time Frame: Day 15, Cycle 1: prior to treatment and 2-4 hours after dose ]
  9. 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 ]
  10. 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 ]
  11. Plasma Concentration of Ipatasertib [ Time Frame: Day 15, Cycle 1: prior to treatment and 1-3 hours after dose ]
  12. 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 ]
  13. Plasma Concentration of CPI-444 [ Time Frame: Day 1, Cycles 2 and 4: prior to treatment and 2-5 hours after dose ]
  14. Plasma Concentration of Linagliptin [ Time Frame: Day 1, Cycle 1: 2 hours post-dose; Day 1 of Cycles 2 and 3: pre-treatment. ]


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 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

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
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United States, Connecticut
Smilow Cancer Hospital at Yale New Haven Recruiting
New Haven, Connecticut, United States, 06510
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749 Recruiting
New York, New York, United States, 10032
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Australia, Victoria
Peter Mac Callum Cancer Center Recruiting
East Melbourne, Victoria, Australia, 3002
France
Centre Léon Bérard Recruiting
Lyon, France, 69008
Hopital de la Timone Recruiting
Marseille, France, 13005
Institut Universitaire du Cancer de Toulouse-Oncopole; PHARMACIE Recruiting
Toulouse, France, 31100
Israel
Rambam Medical Center; Oncology Not yet recruiting
Haifa, Israel, 3109601
Rabin Medical Center Not yet recruiting
Petach Tikva, Israel, 49100
Chaim Sheba Medical Center; Oncology Dept Not yet recruiting
Ramat Gan, Israel, 52620-00
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 03722
University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC) Recruiting
Songpa-gu, Korea, Republic of, 05505
Spain
Clínica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31620
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Fundación Jimenez Díaz Recruiting
Madrid, Spain, 28040
South Texas Accelerated Research Therapeutics Madrid - CIOCC - Universitario Sanchinarro Recruiting
Madrid, Spain, 28050
United Kingdom
Barts Cancer Institute Recruiting
London, United Kingdom, E1 2AT
Royal Marsden Hospital; Institute of Cancer Research Recruiting
Sutton, United Kingdom, SM2 5PT
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     History of Changes
Other Study ID Numbers: BO39610
2017-001267-21 ( EudraCT Number )
First Posted: November 9, 2017    Key Record Dates
Last Update Posted: October 31, 2019
Last Verified: October 2019

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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
Carboplatin
Docetaxel
Pemetrexed
Atezolizumab
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators