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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03337698




Registration number
NCT03337698
Ethics application status
Date submitted
7/11/2017
Date registered
9/11/2017
Date last updated
17/03/2020

Titles & IDs
Public title
A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
Scientific 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)
Secondary ID [1] 0 0
2017-001267-21
Secondary ID [2] 0 0
BO39610
Universal Trial Number (UTN)
Trial acronym
Morpheus Lung
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Cobimetinib
Treatment: Drugs - RO6958688
Treatment: Drugs - Docetaxel
Treatment: Drugs - CPI-444
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Carboplatin
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Linagliptin
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Ipatasertib
Treatment: Drugs - Idasanutlin
Treatment: Drugs - Bevacizumab

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: Cobimetinib
Cobimetinib is administered orally on Days 1-21 of a 28 day cycle.

Treatment: Drugs: 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

Treatment: Drugs: 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.

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

Treatment: Drugs: Pemetrexed
Pemetrexed is administered by IV on Day 1 of a 21 day cycle.

Treatment: Drugs: Carboplatin
Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day cycle.

Treatment: Drugs: Gemcitabine
Gemcitabine is administered by IV on Days 1 and 8 of the first 4 or 6 cycles out of a 21 day cycle

Treatment: Drugs: Linagliptin
Linagliptin is administered orally once daily on Days 1 to 21 out of a 21 day cycle

Treatment: Drugs: Tocilizumab
Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms.

Treatment: Drugs: Ipatasertib
Ipatasertib will be administered orally once a day on Days 1-21 of each 28-day cycle.

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

Treatment: Drugs: Bevacizumab
Bevacizumab is administered by IV on Day 1 of each 21-day cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Objective Response
Timepoint [1] 0 0
Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter
Secondary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Randomization to the first occurrence of disease progression or death from any cause (up to approximately 3-5 years)
Secondary outcome [2] 0 0
Overall Survival After Randomization
Timepoint [2] 0 0
Randomization to death from any cause (up to approximately 3-5 years)
Secondary outcome [3] 0 0
Percentage of Participants Who Are Alive at Month 6 and at Month 12
Timepoint [3] 0 0
Month 6, Month 12
Secondary outcome [4] 0 0
Duration of Response
Timepoint [4] 0 0
First occurrence of a documented objective response to disease progression or death (up to approximately 3-5 years)
Secondary outcome [5] 0 0
Disease Control
Timepoint [5] 0 0
Randomization to the first occurrence of disease progression or death from any cause (up to approximately 3-5 years)
Secondary outcome [6] 0 0
Percentage of Participants with Adverse Events
Timepoint [6] 0 0
Baseline through the end of the study (approximately 3-5 years)

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter Mac Callum Cancer Center - East Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
France
State/province [5] 0 0
Lyon
Country [6] 0 0
France
State/province [6] 0 0
Marseille
Country [7] 0 0
France
State/province [7] 0 0
Toulouse
Country [8] 0 0
Israel
State/province [8] 0 0
Haifa
Country [9] 0 0
Israel
State/province [9] 0 0
Petach Tikva
Country [10] 0 0
Israel
State/province [10] 0 0
Ramat Gan
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Songpa-gu
Country [13] 0 0
Spain
State/province [13] 0 0
Navarra
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
United Kingdom
State/province [16] 0 0
London
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03337698
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BO39610 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03337698