Primary Efficacy ObjectivesUnless otherwise specified, efficacy objectives will be analyzed for the following two treatment comparisons:• Atezolizumab + carboplatin + paclitaxel + bevacizumab (Arm B) versus carboplatin + paclitaxel + bevacizumab (…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
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
disease progression as determined by the investigator using RECIST v1.1 or
death from any cause, whichever occurs first in the tGE-WT population and the
ITT-WT population
• OS, defined as the time from randomization to death from any cause in the
ITT-WT population
Secondary outcome
The secondary efficacy outcome measures for this study are the following:
• OS in the tGE WT population
• PFS, as determined by the investigator according to RECIST v1.1, and OS in
the TC2/3 or IC2/3 WT population and the TC1/2/3 or IC1/2/3 WT population
• PFS, as determined by the investigator according to RECIST v1.1, and OS in
the tGE population and the ITT population
• Objective response, defined as partial response (PR) or complete response
(CR) as determined by the investigator according to RECIST v1.1 1 in the tGE-WT
population and the ITT-WT population
• DOR, defined as the time interval from 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
1 in the tGE-WT population and the ITT-WT population
• PFS, defined as the time from randomization to the first occurrence of
disease progression as determined by the IRF using RECIST v1.1 or death from
any cause, whichever occurs first 1 in the tGE-WT population and the ITT-WT
population
• OS rates at 1 and 2 years 1 in the tGE-WT population and the ITT-WT population
• PFS, as determined by the investigator according to RECIST v1.1, and OS in
the two atezolizumab-containing arms in the tGE WT population and the ITT WT
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 in the tGE-WT population and the ITT-WT
population
• Change from baseline in patient reported lung cancer symptoms (chest pain,
dyspnea, and cough) on the symptom severity score of the Symptoms in Lung
Cancer scale in the tGE-WT population and the ITT-WT 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
Treatment with MPDL3280A offers the potential for clinical benefit in NSCLC
patients, in addition to platinum-based chemotherapy with or without
bevacizumab.
Study objective
Primary Efficacy Objectives
Unless otherwise specified, efficacy objectives will be analyzed for the
following two treatment comparisons:
• Atezolizumab + carboplatin + paclitaxel + bevacizumab (Arm B) versus
carboplatin + paclitaxel + bevacizumab (Arm C)
• Atezolizumab + carboplatin + paclitaxel (Arm A) versus carboplatin +
paclitaxel + bevacizumab (Arm C)
The term *wild type* (WT) refers to randomized patients who do not have a
sensitizing EGFR mutation or ALK translocation.
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 immune cells
(ICs), as analyzed through use of a centrally performed IHC test.
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 RECIST v1.1 in the tGE-WT
population and the ITT-WT population
• To evaluate the efficacy of atezolizumab as measured by overall survival (OS)
in the ITT-WT population
Secondary Efficacy Objectives
The secondary efficacy objectives for this study are the following:
• To evaluate the efficacy of atezolizumab as measured by OS in the tGE WT
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 WT population and the
TC1/2/3 or IC1/2/3 WT population
• To evaluate the efficacy of atezolizumab as measured by investigator-assessed
PFS according to RECIST v1.1 and OS in the tGE population and the ITT population
• To evaluate the efficacy of atezolizumab as measured by investigator assessed
objective response rate (ORR) according to RECIST v1.1 in the tGE-WT population
and the ITT-WT population
• To evaluate the efficacy of atezolizumab as measured by investigator assessed
duration of response (DOR) according to RECIST v1.1 in the tGE-WT population
and the ITT-WT population
• To evaluate the efficacy of atezolizumab as measured by an Independent Review
Facility (IRF)-assessed PFS according to RECIST v1.1 in the tGE-WT population
and the ITT-WT population
• To evaluate the OS rate at 1 and 2 years in each treatment arm for the tGE-WT
population and the ITT-WT population
• To compare the efficacy of the two atezolizumab-containing arms, Arm A versus
Arm B, as measured by investigator assessed PFS according to RECIST v1.1 and
by OS in the tGE-WT population and the ITT-WT population
• 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-WT population and the ITT-WT population
• To determine the impact of atezolizumab as measured by change in 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 for the
tGE-WT population and the ITT-WT
The safety objectives for this study are:
• To evaluate the safety and tolerability of atezolizumabin each of the two
treatment comparisons described in Section 2.1.1
• To evaluate the incidence and titers of ATAs against atezolizumab and to
explore the potential relationship of the immunogenicity response with
pharmacokinetics, safety, and efficacy
The PK objectives for this study are:
• To characterize the pharmacokinetics of atezolizumab when given in
combination with carboplatin andpaclitaxel with and without bevacizumab (Arms A
and B)
• To characterize the pharmacokinetics of carboplatin when given in combination
with paclitaxel with and without atezolizumab and/ or bevacizumab (Arms A, B,
and C)
• To characterize the pharmacokinetics of paclitaxel when given in combination
with carboplatin with and without atezolizumab and/ or bevacizumab (Arms A, B,
and C)
• To characterize the pharmacokinetics of bevacizumab when given in combination
with carboplatin and paclitaxel with and without atezolizumab (Arms B and C)
The exploratory objectives for this study are the following:
• To evaluate the efficacy of atezolizumab as measured by investigator-assessed
time to response (TTR) and time-in-response (TIR) according to RECIST v1.1
• To evaluate ORR and DOR according to RECIST v1.1 as assessed by the IRF
• To evaluate investigator-assessed ORR, PFS, and DOR according to modified
RECIST for the atezolizumab-containing treatment arms
• 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 (IMpower150)
designed to evaluate the safety and efficacy of atezolizumab in combination
with carboplatin + paclitaxel with or without bevacizumab compared with
treatment with carboplatin + paclitaxel + bevacizumab in approximately 1200
chemotherapy-naïve patients with Stage IV non-squamous NSCLC.
Intervention
Test Product (experimental drug)
- MPDL3280A (1200 mg IV) is administered on day 1 of each cycle of 21 days.
MPDL3280A is administered to patients randomized to groups A and B.
Non experimental drugs (Comparator)
- Carboplatin is administered via IV infusion to an initial target area under
the curve (AUC) of 6 mg / ml / min to achieve on day 1 of each cycle of 21
days, at 4 to 6 cycles during the induction phase.
- Paclitaxel (200 mg / m 2 IV) is administered on day 1 of each cycle of 21
days, with 4 or 6 cycles during the induction phase.
- Bevacizumab (15 mg / kg IV) is administered on day 1 of each cycle of 21
days, with 4 or 6 cycles during the induction phase and the treatment phase.
- Carboplatin and paclitaxel are administered to patients in all treatment
groups. Bevacizumab is administered to patients randomized to groups B and C.
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 Bevacizumab described in the study
protocol under chapter 5.1.2 Risks Associated with Bevacizumab.
- Risks (adverse events) associated with Carboplatin are described in the study
protocol under Section 5.1.3 Risks Associated with carboplatin
- Risks (adverse events) related to paclitaxel are described in the study
protocol under chapter 5.1.4 Risks Associated with Pacltaxel.
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.
Lung cancer is the most important cause of deaths by cancer in the world; it is
the most prevalent form of cancer in both men and women. In 2008 lung cancer
was 13% of all new cancer patients.
Promising clinical research data on the area of immunotherapy have shown that
therapies aimed at improving the T-cel response to cancer can result in a
significant chance for a longer survival of patients with phase IV cancer.
Treatment with atezolizumab, next to platinumchemotherapy with or without
bevacizumab, offers the opportunity for clinical advantage in patients with
NSCLC.
In chapter 1.4: Study Rationale and Benefit-Risk Assessment, of the research
protocol the rationale of the study is described.
Grenzacherstrasse 124
Basel 4070
CH
Grenzacherstrasse 124
Basel 4070
CH
Listed location countries
Age
Inclusion criteria
- histologically or cytologically confirmed, Stage IV non-squamous NSCLC (per
the Union Internationale contre le Cancer/American Joint Committee on Cancer
staging system, 7th edition; Detterbeck et al. 2009). Patients with tumors of
mixed histology (i.e., squamous and nonsquamous) are eligible if the major
histological component appears to be non-squamous.
- adequate hematologic and end organ function, defined by the following
laboratory results obtained within 14 days prior to randomization.
- 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.
- any approved anti-cancer therapy, including chemotherapy, or hormonal therapy
within 3 weeks prior to initiation of study treatment; the following exceptions
are allowed:
* hormone-replacement therapy or oral contraceptives
* TKIs approved for treatment of NSCLC discontinued > 7 days prior to
randomization; the baseline scan must be obtained after discontinuation of
prior TKIs.
- women who are pregnant, lactating, or intending to become pregnant during the
study.
- history of severe allergic, anaphylactic, or other hypersensitivity reactions
to chimeric or humanized antibodies or fusion proteins.
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 | EUCTR2014-003207-30-NL |
| ClinicalTrials.gov | NCT02366143 |
| CCMO | NL52180.100.15 |