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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— Morpheus Lung  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03337698
• Other study ID #: BO39610
• Secondary ID: 2017-001267-21
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 2, 2018
• Est. completion date: November 30, 2026

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC). Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of participants with tumor PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC, and Cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression. In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). Participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen (Stage 2).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 675
• Est. completion date: November 30, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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
• 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) or TCs >= 50% or TC3 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
• 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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

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.
• Cobimetinib
Cobimetinib is administered orally on Days 1-21 of a 28 day cycle.
• 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.
• Docetaxel
Docetaxel is administered by IV on Day 1 of each 21 day cycle.
• CPI-444
CPI-444 is administered orally twice daily on Days 1- 21, of a 21 day cycle.
• Pemetrexed
Pemetrexed is administered by IV on Day 1 of a 21 day cycle.
• Carboplatin
Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day cycle.
• Gemcitabine
Gemcitabine is administered by IV on Days 1 and 8 of the first 4 or 6 cycles out of a 21 day cycle.
• Linagliptin
Linagliptin is administered orally once daily on Days 1 to 21 out of a 21 day cycle.
• Tocilizumab
Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms.
• Ipatasertib
Ipatasertib will be administered orally once a day on Days 1-21 of each 28-day cycle.
• Bevacizumab
Bevacizumab is administered by IV on Day 1 of each 21-day cycle.
• Sacituzumab Govitecan
Sacituzumab Govitecan is administered by IV on Day 1 and 8 of each 21-day cycle.

Other:
• Radiation
Radiotherapy up to 21 days

Drug:
• Evolocumab
Evolocumab is administered subcutaneously at a dose of 140 mg on Days 1 and 15 of each 28-day cycle.
• Tiragolumab
Tiragolumab is administered on Day 1 of each 21 day cycle.
• XL092
XL092 is administered orally once a day on Day 1 to Day 21 of a 21 day cycle.
• Camonsertib
Camonsertib is administered orally on Days 1-3, Days 8-10 of a 21 day cycle.

Locations

Country	Name	City	State
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Peter Mac Callum Cancer Center	East Melbourne	Victoria
France	CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre	Bordeaux
France	Centre Georges Francois Leclerc	Dijon
France	Centre Léon Bérard	Lyon
France	Hopital de la Timone	Marseille
France	Institut Régional du Cancer de Montpellier	Montpellier
France	Institut De Cancerologie De L'Ouest; Medical Oncology	Saint Herblain
France	Institut Universitaire du Cancer de Toulouse-Oncopole; PHARMACIE	Toulouse
Israel	Rambam Medical Center; Oncology	Haifa
Israel	Rabin Medical Center	Petach Tikva
Israel	Chaim Sheba Medical Center; Oncology Dept	Ramat Gan
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)	Songpa-gu
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Fundación Jimenez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro-CIOCC	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Clinico Universitario de Valencia	Valencia
Taiwan	National Cheng Kung University Hospital; Gasterointestinal	Tainan City
Taiwan	Taipei Veterans General Hospital	Taipei City
United Kingdom	Barts Cancer Institute	London
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne
United Kingdom	Royal Marsden Hospital; Institute of Cancer Research	Sutton
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University Hospitals Case Medical Center; Seidman Cancer Center	Cleveland	Ohio
United States	Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Smilow Cancer Hospital at Yale New Haven	New Haven	Connecticut
United States	Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749	New York	New York
United States	Christiana Care Health Services	Newark	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  France,  Israel,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Objective Response		Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter
Secondary	Progression Free Survival (PFS)		Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)
Secondary	Overall Survival After Randomization		Randomization to death from any cause (up to approximately 8 years)
Secondary	Percentage of Participants Who Are Alive at Month 6 and at Month 12		Month 6, Month 12
Secondary	Duration of Response		First occurrence of a documented objective response to disease progression or death (up to approximately 8 years)
Secondary	Disease Control		Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)
Secondary	Percentage of Participants with Adverse Events		Baseline through the end of the study (approximately 8 years)