Trial Title:
A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
NCT ID:
NCT03337698
Condition:
Carcinoma, Non-Small-Cell Lung
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Linagliptin
Bevacizumab
Atezolizumab
Carboplatin
Gemcitabine
Docetaxel
Pemetrexed
Ipatasertib
Evolocumab
Sacituzumab govitecan
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of
each 28 day cycle.
Arm group label:
Stage 1: Cohort 1: Atezolizumab
Arm group label:
Stage 1: Cohort 1: Atezolizumab + Cobimetinib
Arm group label:
Stage 1: Cohort 1: Atezolizumab + RO6958688
Arm group label:
Stage 1: Cohort 1: Atezolizumab + Tiragolumab
Arm group label:
Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab
Arm group label:
Stage 1: Cohort 2: Atezolizumab + CPI-444
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Camonsertib
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Cobimetinib
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Docetaxel
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Evolocumab
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Ipatasertib
Arm group label:
Stage 1: Cohort 2: Atezolizumab + RO6958688
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan
Arm group label:
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Arm group label:
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Arm group label:
Stage 2: Cohort 2: Atezolizumab + Docetaxel
Arm group label:
Stage 2: Cohort 2: Atezolizumab + Linagliptin
Arm group label:
Stage 2: Cohort 2: Atezolizumab + RO6958688
Intervention type:
Drug
Intervention name:
Cobimetinib
Description:
Cobimetinib is administered orally on Days 1-21 of a 28 day cycle.
Arm group label:
Stage 1: Cohort 1: Atezolizumab + Cobimetinib
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Cobimetinib
Intervention type:
Drug
Intervention name:
RO6958688
Description:
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.
Arm group label:
Stage 1: Cohort 1: Atezolizumab + RO6958688
Arm group label:
Stage 1: Cohort 2: Atezolizumab + RO6958688
Arm group label:
Stage 2: Cohort 2: Atezolizumab + RO6958688
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Docetaxel is administered by IV on Day 1 of each 21 day cycle.
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Docetaxel
Arm group label:
Stage 1: Cohort 2: Docetaxel
Arm group label:
Stage 2: Cohort 2: Atezolizumab + Docetaxel
Intervention type:
Drug
Intervention name:
CPI-444
Description:
CPI-444 is administered orally twice daily on Days 1- 21, of a 21 day cycle.
Arm group label:
Stage 1: Cohort 2: Atezolizumab + CPI-444
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Pemetrexed is administered by IV on Day 1 of a 21 day cycle.
Arm group label:
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day
cycle.
Arm group label:
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Arm group label:
Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Gemcitabine is administered by IV on Days 1 and 8 of the first 4 or 6 cycles out of a 21
day cycle.
Arm group label:
Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin
Intervention type:
Drug
Intervention name:
Linagliptin
Description:
Linagliptin is administered orally once daily on Days 1 to 21 out of a 21 day cycle.
Arm group label:
Stage 2: Cohort 2: Atezolizumab + Linagliptin
Intervention type:
Drug
Intervention name:
Tocilizumab
Description:
Tocilizumab is administered for the management of cytokine-release syndrome in the
RO6958688-containing arms.
Arm group label:
Stage 1: Cohort 1: Atezolizumab + RO6958688
Arm group label:
Stage 1: Cohort 2: Atezolizumab + RO6958688
Arm group label:
Stage 2: Cohort 2: Atezolizumab + RO6958688
Intervention type:
Drug
Intervention name:
Ipatasertib
Description:
Ipatasertib will be administered orally once a day on Days 1-21 of each 28-day cycle.
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Ipatasertib
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Bevacizumab is administered by IV on Day 1 of each 21-day cycle.
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab
Intervention type:
Drug
Intervention name:
Sacituzumab Govitecan
Description:
Sacituzumab Govitecan is administered by IV on Day 1 and 8 of each 21-day cycle.
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan
Intervention type:
Other
Intervention name:
Radiation
Description:
Radiotherapy up to 21 days
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy
Intervention type:
Drug
Intervention name:
Evolocumab
Description:
Evolocumab is administered subcutaneously at a dose of 140 mg on Days 1 and 15 of each
28-day cycle.
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Evolocumab
Intervention type:
Drug
Intervention name:
Tiragolumab
Description:
Tiragolumab is administered on Day 1 of each 21 day cycle.
Arm group label:
Stage 1: Cohort 1: Atezolizumab + Tiragolumab
Arm group label:
Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab
Intervention type:
Drug
Intervention name:
XL092
Description:
XL092 is administered orally once a day on Day 1 to Day 21 of a 21 day cycle.
Arm group label:
Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib)
Other name:
Zanzalintinib
Intervention type:
Drug
Intervention name:
Camonsertib
Description:
Camonsertib is administered orally on Days 1-3, Days 8-10 of a 21 day cycle.
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib
Arm group label:
Stage 1: Cohort 2: Atezolizumab + Camonsertib
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).
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Smilow Cancer Hospital at Yale New Haven
Address:
City:
New Haven
Zip:
06510
Country:
United States
Facility:
Name:
Christiana Care Health Services
Address:
City:
Newark
Zip:
19713
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
Address:
City:
Las Vegas
Zip:
89169
Country:
United States
Facility:
Name:
Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749
Address:
City:
New York
Zip:
10032
Country:
United States
Facility:
Name:
University Hospitals Case Medical Center; Seidman Cancer Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Facility:
Name:
SCRI Oncology Partners
Address:
City:
Nashville
Zip:
37203
Country:
United States
Facility:
Name:
Blacktown Hospital
Address:
City:
Blacktown
Zip:
2148
Country:
Australia
Facility:
Name:
Peter Mac Callum Cancer Center
Address:
City:
East Melbourne
Zip:
3002
Country:
Australia
Facility:
Name:
CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
Address:
City:
Bordeaux
Zip:
33075
Country:
France
Facility:
Name:
Centre Georges Francois Leclerc
Address:
City:
Dijon
Zip:
21000
Country:
France
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Zip:
69008
Country:
France
Facility:
Name:
Hopital de la Timone
Address:
City:
Marseille
Zip:
13005
Country:
France
Facility:
Name:
Institut Régional du Cancer de Montpellier
Address:
City:
Montpellier
Zip:
34298
Country:
France
Facility:
Name:
Institut De Cancerologie De L'Ouest; Medical Oncology
Address:
City:
Saint Herblain
Zip:
44115
Country:
France
Facility:
Name:
Institut Universitaire du Cancer de Toulouse-Oncopole; PHARMACIE
Address:
City:
Toulouse
Zip:
31100
Country:
France
Facility:
Name:
Rambam Medical Center; Oncology
Address:
City:
Haifa
Zip:
3109601
Country:
Israel
Facility:
Name:
Rabin Medical Center
Address:
City:
Petach Tikva
Zip:
4922297
Country:
Israel
Facility:
Name:
Chaim Sheba Medical Center; Oncology Dept
Address:
City:
Ramat Gan
Zip:
5262100
Country:
Israel
Facility:
Name:
Chonnam National University Hwasun Hospital
Address:
City:
Jeollanam-do
Zip:
58128
Country:
Korea, Republic of
Facility:
Name:
Seoul National University Hospital
Address:
City:
Seoul
Zip:
03080
Country:
Korea, Republic of
Facility:
Name:
Severance Hospital, Yonsei University Health System
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Facility:
Name:
Korea University Guro Hospital
Address:
City:
Seoul
Zip:
08308
Country:
Korea, Republic of
Facility:
Name:
University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)
Address:
City:
Songpa-gu
Zip:
05505
Country:
Korea, Republic of
Facility:
Name:
Clínica Universidad de Navarra
Address:
City:
Pamplona
Zip:
31620
Country:
Spain
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Facility:
Name:
Fundación Jimenez Díaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Facility:
Name:
Hospital Universitario La Paz
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Facility:
Name:
Hospital Universitario HM Sanchinarro-CIOCC
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Facility:
Name:
Hospital Regional Universitario de Malaga
Address:
City:
Malaga
Zip:
29010
Country:
Spain
Facility:
Name:
Hospital Clinico Universitario de Valencia
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Facility:
Name:
National Cheng Kung University Hospital; Gasterointestinal
Address:
City:
Tainan City
Zip:
704
Country:
Taiwan
Facility:
Name:
Taipei Veterans General Hospital
Address:
City:
Taipei City
Zip:
11217
Country:
Taiwan
Facility:
Name:
Barts Cancer Institute
Address:
City:
London
Zip:
E1 2AT
Country:
United Kingdom
Facility:
Name:
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Address:
City:
Newcastle upon Tyne
Zip:
NE7 7DN
Country:
United Kingdom
Facility:
Name:
Royal Marsden Hospital; Institute of Cancer Research
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Start date:
January 2, 2018
Completion date:
November 30, 2026
Lead sponsor:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
Hoffmann-La Roche
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT03337698
