Unless otherwise specified, efficacy objectives will be analyzed for the following two treatment comparisons:• Atezolizumab + carboplatin + nab-paclitaxel (Arm B) versus carboplatin + nab- paclitaxel (Arm C)• Atezolizumab + carboplatin + paclitaxel…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms benign (excl mesotheliomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The co-primary efficacy outcome measures for this study are the following:
• PFS, defined as the time from randomization to the first occurrence of the
disease progression as determined by the investigator using RECIST v1.1 or
death from any cause, whichever occurs first in the tGE population and ITT
population
• OS, defined as the time from randomization to death from any cause in the ITT
population
Secondary outcome
The secondary efficacy outcome measures for this study are the following:
• OS in the tGE population
• PFS, as determined by the investigator according to RECIST v1.1, and OS in
the TC2/3 or IC2/3 population and the TC1/2/3 or IC1/2/3 population
• Objective response, defined as partial response (PR) or complete response
(CR) as determined by the investigator according to RECIST v1.1 in the tGE
population and ITT population
• DOR, defined as the time interval from the first occurrence of a documented
objective response to the time of disease progression as determined by the
investigator using RECIST v1.1, or death from any cause, whichever occurs first
in the tGE population and ITT population
• OS rates at 1 and 2 years for the tGE population and ITT population
• 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], dyspnea
[multi-item subscale], chest pain, and arm/shoulder pain) in the tGE population
and ITT population
• Change from baseline in patient reported lung cancer symptoms (cough,
dyspnea, and chest pain) on the symptom severity score of the SILC scale in the
tGE population and ITT population
• PFS, as determined by the investigator according to RECIST v1.1, and OS in
the two atezolizumab-containing arms in the tGE population and the ITT
population
Background summary
Lung cancer remains the leading cause of cancer deaths worldwide; it is the
most common cancer in both men and women and accounted for approximately 13% of
all new cancers in 2008. Encouraging clinical data emerging in the field of
tumor immunotherapy have demonstrated that therapies focused on enhancing
T-cell responses against cancer can result in a significant survival benefit in
patients with Stage IV cancer
Study objective
Unless otherwise specified, efficacy objectives will be analyzed for the
following two treatment comparisons:
• Atezolizumab + carboplatin + nab-paclitaxel (Arm B) versus carboplatin + nab-
paclitaxel (Arm C)
• Atezolizumab + carboplatin + paclitaxel (Arm A) versus carboplatin + nab-
paclitaxel (Arm C)
The term *tumor gene expression* (tGE) refers to randomized patients with a
defined level of expression of a PD-L1 and T-effector gene signature in tumor
tissue, as analyzed through use of a centrally performed RNA-based assay.
Some efficacy endpoints will be analyzed in a population of randomized patients
with a defined level of PD-L1 expression on tumor cells (TCs) and
tumor-infiltrating immune cells (ICs), as analyzed through use of a centrally
performed immunohistochemistry (IHC) test.
Efficacy Objectives
The co-primary objectives of this study are the following:
• To evaluate the efficacy of atezolizumab as measured by investigator assessed
progression-free survival (PFS) according to Response Evaluation Criteria in
Solid Tumors, Version 1.1 (RECIST v1.1) in the tGE population and the
intent-to-treat (ITT) population
• To evaluate the efficacy of atezolizumab as measured by overall survival (OS)
in the ITT population
The secondary efficacy objectives for this study are the following:
• To evaluate the efficacy of atezolizumab as measured by OS in the tGE
population
• To evaluate the efficacy of atezolizumab as measured by investigator-assessed
PFS according to RECIST v1.1 and OS in the TC2/3 or IC2/3 population and the
TC1/2/3 or IC1/2/3 population
• To evaluate the efficacy of atezolizumab as measured by investigator assessed
objective response rate (ORR) according to RECIST v1.1 in the tGE population
and the ITT population
• To evaluate the efficacy of atezolizumab as measured by investigator assessed
duration of response (DOR) according to RECIST v1.1 in the tGE population and
the ITT population
• To evaluate the OS rate at 1 and 2 years in each treatment arm for the tGE
population and the ITT population n
• To determine the impact of atezolizumab as measured by time to deterioration
(TTD) in patient reported lung cancer symptoms of cough, dyspnea (single item
and multi item subscales), chest pain, or arm/shoulder pain, using the European
Organisation for the Research and Treatment of Cancer (EORTC) Quality-of-Life
Questionnaire-Core (QLQ C30) and the supplemental lung cancer module (QLQ LC13)
in the tGE population and the ITT population
• To determine the impact of atezolizumab as measured by change from baseline
(i.e., improvement or deterioration based upon presenting symptomatology) in
patient reported lung cancer symptom (chest pain, dyspnea, and cough) score
using the Symptoms in Lung Cancer (SILC) scale symptom severity score in the
tGE population and the ITT population
• To evaluate the efficacy of the treatment regimen of atezolizumab +
carboplatin + paclitaxel versus atezolizumab + carboplatin + nab paclitaxel as
measured by investigator assessed PFS according to RECIST v1.1 and OS in the
tGE population and the ITT population
The safety objectives for this study are the following:
• To evaluate the safety and tolerability of atezolizumab in each of the two
treatment comparisons
• To evaluate the incidence and titers of anti-therapeutic antibodies (ATAs)
against atezolizumab and to explore the potential relationship of the
immunogenicity response with pharmacokinetics, safety, and efficacy
The pharmacokinetic (PK) objectives for this study are the following:
• To characterize the pharmacokinetics of atezolizumab when given in
combination with carboplatin + paclitaxel (Arm A) or with carboplatin +
nab-paclitaxel (Arm B)
• To characterize the pharmacokinetics of carboplatin when given in combination
with paclitaxel and atezolizumab (Arm A) or with nab-paclitaxel with and
without atezolizumab (Arms B and C)
• To characterize the pharmacokinetics of paclitaxel when given in combination
with atezolizumab and carboplatin (Arm A)
• To characterize the pharmacokinetics of nab-paclitaxel (reported as total
paclitaxel) when given in combination with carboplatin with and without
atezolizumab (Arms B and C)
The exploratory objectives for this study are the following:
• To evaluate PFS at 6 months and at 1 year in each treatment arm
• To evaluate the OS rate at 3 years in each treatment arm
• To assess predictive, prognostic, and pharmacodynamic exploratory biomarkers
in archival and/or fresh tumor tissue and blood and their association with
disease status, mechanisms of resistance, and/or response to study treatment
• To evaluate the utility of biopsy at the time of apparent disease progression
to distinguish apparent increases in tumor volume related to the
immunomodulatory activity of atezolizumab (i.e., pseudoprogression/tumor immune
infiltration) from true disease progression
• To evaluate and compare patient*s health status as assessed by the EuroQoL 5
Dimensions 3-Level (EQ-5D 3L) questionnaire to generate utility scores for use
in economic models for reimbursement
• To determine the impact of atezolizumab as measured by change from baseline
in patient-reported outcomes of health-related quality of life, lung
cancer-related symptoms, and functioning as assessed by the EORTC QLQ C30 and
LC13
Study design
This is a randomized, Phase III, multicenter, open-label study (IMpower131)
designed to evaluate the safety and efficacy van atezolizumab (ANTI-PD-L1
ANTIBODY) in combination with CARBOPLATIN + PACLITAXEL or atezolizumab IN
COMBINATION with CARBOPLATIN + NAB PACLITAXEL VERSUS CARBOPLATIN +
NAB-PACLITAXEL in chemotherapy naive patients with stage IV Squamous Non-small
Cell Lung cancer.
Intervention
Investigational Medicinal Products Test Product (Investigational Drug)
MPDL3280A (1200 mg IV) will be administered on Day 1 of each 21-day cycle.
Non-Investigational Medicinal Products Comparator
- Carboplatin will be administered by IV infusion to achieve an initial target
area under the curve (AUC) of 6 mg/mL/min on Day 1 of each 21-day cycle for 4
or 6 cycles during the induction phase
- Nab-paclitaxel (100 mg/m2 IV) will be administered on Days 1, 8, and 15 of
each 21-day cycle for 4 or 6 cycles during the induction phase.
- Paclitaxel (200 mg/m2 IV) will be administered on Day 1 of each 21-day cycle
for 4 or 6 cycles during the induction phase. Carboplatin and paclitaxel will
be administered to patients randomized to Arm A.
Carboplatin and nab-paclitaxel will be administered to patients in Arms B and
C. Nab-paclitaxel will be considered an IMP for study purposes in countries
where nab-paclitaxel is considered an IMP by local regulations.
Study burden and risks
- Risks (adverse events) related to atezolizumab described in the study
protocol under chapter 5.1.1 Risks Associated with atezolizumab.
- Risks(adverse events) associated with carboplatine described in the study
protocol under chapter 5.1.2 Risks Associated with carboplatine.
- Risks (adverse events) associated with paclitaxel are described in the study
protocol under Section 5.1.3 Risks Associated with paclitaxel
- Risks (adverse events) related to nab-paclitaxel are described in the study
protocol under chapter 5.1.4 Risks Associated with nab-paclitaxel
Besides the possible adverse reactions as described in the study protocol, the
collection of blood samples can cause mild pain, redness, bruising and or
irritation at the injection site. CT examinations may be uncomfortable for a
patient and CT examinations that require a contrast injection may cause slight,
temporary discomfort while the intravenous needle is placed.
Lungcancer remains the most important cause of death by cancer in the world; it
is the most prevalent form of cancer in both men and women. In 2008 lungcancer
was 13% of all new cancer patients. Promising clinical research data op the
area of immunotherapy have shown that therapies aimed at improving the T-cell
response to cancer can result in a significant chance of longer survival in
patients with phase IV cancer. The treatment with atezolizumab, next to
platinumchemotherapy, offers the opportunity for clinical advantage in NSCLC
patients.
In chapter 1.4: Study Rationale and Benefit-Risk Assessment, of the study
protocol the rationale of the research is described.
Grenzacherstrasse 124
Basel 4070
CH
Grenzacherstrasse 124
Basel 4070
CH
Listed location countries
Age
Inclusion criteria
• ECOG performance status of 0 or 1
• Histologically or cytologically confirmed, Stage IV squamous NSCLC
• No prior treatment for Stage IV squamous NSCLC
Patients with a sensitizing mutation in the EGFR gene must have
experienced disease progression (during or after treatment) or
intolerance to treatment with erlotinib, gefitinib, or another EGFR
tyrosine kinase inhibitor (TKI) appropriate for the treatment of EGFRmutant
NSCLC.
Patients with an ALK fusion oncogene must have experienced disease
progression (during or after treatment) or intolerance to treatment with
one or more ALK inhibitors (i.e. crizotinib) appropriate for the treatment
of NSCLC in patients having an ALK fusion oncogene.
• Patients who have received prior neo-adjuvant, adjuvant radiotherapy, chemotherapy, or chemoradiotherapy with curative intent for nonmetastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy or completion of chemoradiotherapy.
• Measurable disease, as defined by RECIST v1.1
Exclusion criteria
• Active or untreated CNS metastases as determined by CT or MRI
evaluation during screening and prior radiographic assessments
• Spinal cord compression not definitively treated with surgery and/or
radiation or previously diagnosed and treated spinal cord compression
without evidence that disease has been clinically stable for > 2 weeks
prior to randomization
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring
recurrent drainage procedures (once monthly or more frequently)
• History of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or fusion proteins
• Positive test for HIV
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003208-59-NL |
| ClinicalTrials.gov | NCT02367794 |
| CCMO | NL52156.100.15 |