Clinical trial NCT03337698: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-11-09
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


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
* 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

Primary outcomes:
measure: Percentage of Participants with Objective Response
timeFrame: Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)
measure: Overall Survival After Randomization
timeFrame: Randomization to death from any cause (up to approximately 8 years)
measure: Percentage of Participants Who Are Alive at Month 6 and at Month 12
timeFrame: Month 6, Month 12
measure: Duration of Response
timeFrame: First occurrence of a documented objective response to disease progression or death (up to approximately 8 years)
measure: Disease Control
timeFrame: Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline through the end of the study (approximately 8 years)
Other outcomes:
Locations:
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
state: Nevada
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: East Melbourne
country: Australia
facility: Peter Mac Callum Cancer Center
state: Victoria
city: Bordeaux
country: France
facility: CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hopital de la Timone
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier
city: Saint Herblain
country: France
facility: Institut De Cancerologie De L'Ouest
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse-Oncopole
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Songpa-gu
country: Korea, Republic of
facility: University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Fundación Jimenez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro-CIOCC
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: London
country: United Kingdom
facility: Barts Cancer Institute
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: