Study to evaluate the safety and efficacy of MPDL3280A (anti-PDL1 antibody) compared to platinum-based chemotherapy in patients with metastatic, non-squamous, PD-L1-selected, non-small cell lung cancer that has not been treated with chemotherapy.

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2014-003083-21-ES
• Date of registration: 01/06/2015
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: Study to evaluate the safety and efficacy of MPDL3280A (anti-PDL1 antibody) compared to platinum-based chemotherapy in patients with metastatic, non-squamous, PD-L1-selected, non-small cell lung cancer that has not been treated with chemotherapy.
• Scientific title: A PHASE III, OPEN-LABEL, RANDOMIZED STUDY OF MPDL3280A (Anti?PDL1 ANTIBODY) COMPARED WITH CISPLATIN OR CARBOPLATIN+PEMETREXED FOR PD-L1?SELECTED CHEMOTHERAPY NAIVE PATIENTS WITH STAGE IV NON-SQUAMOUS NON?SMALL CELL LUNG CANCER
• Date of first enrolment: 24/06/2015
• Target sample size: 400
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003083-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Brazil, Canada, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Philippines, Poland, Romania, Russian Federation, Serbia, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
?ECOG performance status of 0 or 1
?Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
?No prior treatment for Stage IV non-squamous NSCLC, unless patient had a previously detected sensitizing EGFR mutation or ALK fusion oncogene
oPatients with a known sensitizing mutation in the EGFR gene or ALK fusion oncogene must have experienced disease progression or intolerance to treatment any EGFR TKI approved for the treatment of EGFR-mutant NSCLC or any ALK inhibitor approved for the treatment of NSCLC in patients having an ALK fusion oncogene, respectively.
?Patient with a history of treated asymptomatic CNS metastases
?Tumor PD-L1 expression as determined by an IHC assay performed by a central laboratory on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
?Measurable disease, as defined by RECIST v1.1
?Adequate hematologic and end-organ function
?For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception and to continue its use for 90 days after the last dose of MPDL3280A
?Women who are not postmenopausal (? 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
?Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
?Leptomeningeal disease
?Uncontrolled tumor-related pain
?Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
?Uncontrolled or symptomatic hypercalcemia
?Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death
?History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener?s granulomatosis, Sjögren?s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
?History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
?Positive test for HIV
?Patients with active hepatitis B or hepatitis C
?Active tuberculosis
?Severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
?Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
?Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
?Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to randomization
?Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies
?Treatment with systemic immunostimulatory agents (including but not limited to interferons, IL-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to randomization
?Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to randomization


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Stage IV, Non-Squamous, Non-Small Cell Lung Cancer
MedDRA version: 18.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: MPDL3280A-RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not Yet defined
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Main Objective: The primary objective for this study is to evaluate the efficacy of MPDL3280A compared with carboplatin or cisplatin + pemetrexed in chemotherapy-naive patients with Stage IV non squamous NSCLC, as measured by investigator-assessed PFS according to RECIST v1.1

Primary end point(s): ?PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first

Secondary Objective: To evaluate the efficacy of MPDL3280A compared with carboplatin or cisplatin + pemetrexed as measured by ORR according to RECIST v1.1 assessed by investigator
To evaluate the efficacy of MPDL3280A compared with carboplatin or cisplatin + pemetrexed as measured by OS
To determine the impact of MPDL3280A compared with carboplatin or cisplatin +pemetrexed as measured by time to deterioration (TTD) in patient reported lung cancer symptom (cough, dyspnea, chest pain) score
To evaluate the efficacy of MPDL3280A compared with carboplatin or cisplatin + pemetrexed as measured by Independent Review Facility (IRF)-assessed PFS according to RECIST v1.1
To evaluate the efficacy of MPDL3280A as measured by investigator-assessed DOR according to RECIST v1.1
To evaluate the efficacy of MPDL3280A as measured by investigator-assessed time in response (TIR) according to RECIST v1.1
To evaluate the OS rate at 1 and 2 years in each treatment arm

Timepoint(s) of evaluation of this end point: Please refer to E.5.1

Secondary Outcome(s)

Secondary end point(s): ?Objective response, defined as PR plus CR as determined by the investigator according to RECIST v1.1
?OS, defined as the time from randomization to death from any cause
?TTD in patient reported lung cancer symptoms (cough, dyspnea, or chest pain, whichever occurs first) with use of the SILC scale symptom score, defined as time from randomization to the first deterioration maintained for two assessments or one assessment followed by death from any cause within 1 week
?PFS, defined as the time from randomization to the first occurrence of disease progression as determined by IRF using RECIST v1.1 or death from any cause, whichever occurs first
?DOR, defined as the time from the first occurrence of a documented objective response to the time of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first
?TIR, defined as the same as DOR for responders. For non-responders, TIR is defined as date of randomization plus 1 day.
?1-year OS and 2-year OS
?TTD in patient reported lung cancer symptoms, defined as time from randomization to deterioration (10 point change) on each of the EORTC QLQ-C30 and EORTC QLQ-LC13 symptom subscales (cough, dyspnea [single item and multi item subscales], chest pain, arm/shoulder pain, or fatigue) maintained for two assessments or one assessment followed by death from any cause within 3 weeks
?Change from baseline in patient-reported lung cancer symptoms (chest pain, dyspnea, and cough) on the symptom severity score of the SILC scale

Timepoint(s) of evaluation of this end point: Please refer to E.5.2

Secondary ID(s)

GO29431

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd