The co-primary objectives of this study are: * To evaluate the efficacy of as measured by investigator-assessed PFS according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). * To evaluate the efficacy of atezolizumab as…
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:
* 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. Patients who have not experienced
disease progression or death at the time of analysis will be censored at the
time of last tumor assessment. Patients with no post-baseline tumor assessment
will be censored at the randomization date plus 1 day.
* OS, defined as the time from randomization to death from any cause
Secondary outcome
The secondary efficacy outcome measures for this study are:
* Objective response, defined as PR or CR as determined by the investigator
according to RECIST v1.1
* 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 comes first
* OS at 1 and 2 year landmark timepoints
* 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
* Change from baseline in patient reported lung cancer symptoms (cough,
dyspnea, or chest pain) with use of the SILC scale symptom score
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. Non-small cell lung cancer (NSCLC) is the predominant
subtype of lung cancer, accounting for approximately 85% of all cases.
Research therapies have shown that focused on enhancing T cell responses
against cancer, can result in a significant survival benefit in patients with
Stage IV cancer.
This study is designed to evaluate whether the anti tumor effect seen in
atezolizumab-treated patients would translate into statistically significant
and clinically relevant improvement in PFS and OS when used in combination with
carboplatin or cisplatin + pemetrexed compared with carboplatin or cisplatin +
pemetrexed . This study will allow for the evaluation of the efficacy of
atezolizumab in both the ITT population, as well as in patients with PD
L1-selected tumors
Study objective
The co-primary objectives of this study are:
* To evaluate the efficacy of as measured by investigator-assessed PFS
according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST
v1.1).
* To evaluate the efficacy of atezolizumab as measured by overall survival
(OS).
The secondary efficacy objectives for this study are:
* To evaluate the efficacy of atezolizumab as measured by investigator-assessed
objective response rate (ORR) according to RECIST v1.1
* To evaluate the efficacy of atezolizumab as measured by
investigator-assessed duration of response (DOR) according to RECIST v1.1
* To evaluate the OS rate at 1 and 2 years
* To determine the impact of atezolizumab as measured by the change from
baseline in patient reported lung cancer symptoms of cough, dyspnea (single
item and multi item subscales), chest pain, or arm/shoulder pain, using the
European Organization for the Research and Treatment of Cancer (EORTC)
Quality-of-Life Questionnaire-Core 30 (QLQ-C30) and the supplemental lung
cancer module (QLQ LC13)
* To determine the impact of atezolizumab in each of the treatment regimens as
measured by the change from baseline in patient reported lung cancer symptoms
(chest pain, dyspnea, and cough) scores using the Symptoms in Lung Cancer
(SILC) scale symptom severity scores
Safety Objectives The safety objectives for this study are:
* To evaluate the safety and tolerability of atezolizumab when giving in
combination with carboplatin or cisplatin + pemetrexed or as maintenance
therapy with pemetrexed alone
* To evaluate the incidence and titers of anti-therapeutic antibody (ATAs)
against atezolizumab and to explore the potential relationship of the
immunogenicity response with pharmacokinetics, safety, and efficacy
Pharmacokinetic Objectives The PK objectives for this study are:
* To characterize the pharmacokinetics of atezolizumab when given in
combination with carboplatin or cisplatin + pemetrexed or pemetrexed alone
* To characterize the pharmacokinetics of carboplatin when given in combination
with atezolizumab and pemetrexed
* To characterize the pharmacokinetics of cisplatin when given in combination
with atezolizumab + pemetrexed
* To characterize the pharmacokinetics of pemetrexed when given in combination
with atezolizumab + carboplatin or cisplatin
Exploratory Objectives The exploratory objectives for this study are:
* To evaluate the PFS rate at 6 month and 1-year langmark timepoints
* To evaluate the OS rate at 3 years in each treatment arm
* To evaluate the efficacy of atezolizumab as measured by OS and
investigator-assessed PFS according to RECIST v1.1 in subgroups based on
demographic and baseline characteristics
* To evaluate the efficacy of atezolizumab as measured by milestone survival
* To evaluate the relationship between biomarkers in tumors and blood
(including, but not limited to PD L1, programmed death-1 (PD-1), somatic
mutations and others), as defined by immunohistochemistry (IHC), quantitative
reverse transcriptase-polymerase chain reaction (qRT-PCR), next-generation
sequencing (NGS), and/or other methods and measures of efficacy
* 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 and compare patient*s health status as assessed by the EuroQoL 5
Dimensions 5-Level questionnaire to generate utility scores for use in economic
models for reimbursement
* To determine the impact of atezolizumab in each of the treatment comparisons
as measured by change from baseline in patient-reported outcomes (PROs) of
health-related quality of life, lung cancer related symptoms, and health status
as assessed by the EORTC QLQ-C30 and QLQ-LC13
Study design
This is a randomized, Phase III, multicenter, open-label (IMpower 132) study
designed to evaluate the safety and efficacy of atezolizumab in combination
with cisplatin or carboplatin + pemetrexed compared with treatment with
cisplatin or carboplatin + pemetrexed in patients who are chemotherapy naive
and have Stage IV non squamous NSCLC. Eligible patients will be stratified by
sex (male vs. female), smoking status (never vs. current and/or former),
Eastern Cooperative Oncology Group (ECOG) performance status 0 vs.1
chemotherapy regimen (carboplatin vs. cisplatin)randomized by a 1:1 ratio to
receive one of the following treatment regimens:
* Induction phase (four or six 21-day cycles):
Arm A: Atezolizumab + carboplatin or cisplatin + pemetrexed
Arm B: Carboplatin or cisplatin + pemetrexed
* Maintenance phase (21-day cycles):
Arm A: Atezolizumab + pemetrexed
Arm B: pemetrexed
Treatment with chemotherapy (both in Arm A and B) should be discontinued in all
patients who exhibit evidence of progressive disease by RECIST 1.1. During
induction or maintenance treatment, patients randomized to Arm A may continue
treatment with atezolizumab beyond progressive disease by RECIST v1.1, provided
they are experiencing clinical benefit as assessed by the investigator.
Patients will undergo tumor assessments at baseline and every 6 weeks for the
first 48 weeks following Cycle 1, Day 1, regardless of dose delays. After the
completion of the Week 48 tumor assessment,, tumor assessment will be required
every 9 weeks. Patients will undergo tumor assessments until radiographic
disease progression per RECIST v1.1 or loss of clinical benefit (for
atezolizumab treated only patients who continue treatment after radiographic
disease progression according to RECIST v1.1), withdrawal of consent, study
termination by Sponsor, or death, whichever occurs first. Patients who
discontinue treatment for reasons other than radiographic disease progression
(e.g., toxicity) will continue scheduled tumor assessments until radiographic
disease progression per RECIST v1.1 or loss of clinical benefit (for
atezolizumab treated patients who continue treatment after radiographic disease
progression according to RECIST v1.1), withdrawal of consent, study termination
by Sponsor, or death, whichever occurs first, regardless of whether patients
start a new anti-cancer therapy. All primary imaging data used for tumor
assessment will be collected by the Sponsor to enable centralized, independent
review of response endpoints. The independent reviews of stored scans will be
performed when requested.
Intervention
During this study, the patient will be randomly assigned (by chance) to one of
the two treatment possibilities (called *treatment arms*). The patient will
have a 1 in 2 (50%) chance of being assigned to Arm A or Arm B.
Patients randomized to atezolizumab will receive 1200 mg of atezolizumab
administered by IV infusion every 21 days in a monitored setting where there is
immediate access to trained personnel and adequate equipment/medicine to manage
potentially serious reactions.
Institutions should follow their standard administration regimens for
pemetrexed. The premedication doses administered should be in compliance with
the Summary of Product Characteristics.
Cisplatin will be administered by IV infusion approximately 30 minutes after
completion of the pemetrexed infusion at a dose of 75 mg/m² over 1*2 hours or
per standard of care at the institution. Patients must receive adequate
anti-emetic treatment and appropriate hydration prior to and/or after receiving
cisplatin.
Carboplatin should be administered 30 minutes after completion of pemetrexed
administration by IV infusion over 30-60 minutes to achieve an initial target
area under the concentration time curve (AUC) of 6 mg/mL/min (Calvert formula
dosing) with standard anti emetics per local practice guidelines
Study burden and risks
The required study drug can cause side effects.
- Risks (adverse events) related to MPDL3280A described in the study protocol
under chapter 5.1.1 Risks Associated with MPDL3280A.
- Risks (adverse events) associated with carboplatine described in the study
protocol under chapter 5.1.3 Risks Associated with carboplatine.
- Risks (adverse events) associated with ciplatine are described in the study
protocol under Section 5.1.4 Risks Associated with ciplatine
- Risks (adverse events) related to pemetrexed are described in the study
protocol under chapter 5.1.2 Risks Associated with pemetrexed
Possible Risks and Discomfort Associated with drawing blood
During this study, small amounts of blood will be taken from a vein and used
for tests that allow the patients study doctors to see how you are doing.
Taking blood may cause pain where the needle is inserted, and there is a small
risk of bruising or infection at the place where the needle is inserted. Some
people experience dizziness, upset stomach, or fainting when their blood is
taken.
Possible Risks and Discomfort Associated with Biopsies
As with any procedure, there are risks and discomforts. The patient may feel
some amount of pain or discomfort during the biopsy sample collection,
including slight stinging pain when a local anesthetic is injected by needle to
numb the area, pressure and dull pain where the biopsy needle is inserted,
discomfort from lying still for an extended time, and soreness at the biopsy
sample site. If a general anesthetic is used, the patient will not feel pain
during the procedure because the patient will be asleep. The doctor will
explain the risks of the biopsy procedure to the patient to decide if you want
to participate.
Benefit
Atezolizumab is an antibody (a protein used by the patients body's immune
system to identify and neutralize foreign objects such as bacteria, viruses,
and tumor cells) that affects the patients immune system by blocking a pathway
that is involved in decreasing the patients body*s natural immune response to
fight cancer. By blocking this pathway, atezolizumab may help the patients
immune system stop or reverse the growth of tumors.
Grenzacherstrasse 124
Basel 4070
CH
Grenzacherstrasse 124
Basel 4070
CH
Listed location countries
Age
Inclusion criteria
- Male or female, 18 years of age or older
- Eastern Cooperative Oncology Group (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
- Patients who have received prior neo-adjuvant, adjuvant 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 dose of chemotherapy and/or radiotherapy
-Measurable disease, as defined by RECIST v1.1
- Adequate hematologic and end organ function
- For patients enrolled in the extended China enrollment phase: current
residence of mainland China, Hong Kong, or Taiwan and of Chinese ancestry.
- For women of childbearing potential: agreement to remain abstinent or use
contraceptive methods that result in a failure rate of < 1% per year during the
treatment period and for at least 5 months after the last dose of ATZ and 6
months after the last dose of cisplatin, cisplatin, carboplatin, or pemetrexed.
Women must refrain from donating eggs during this same period.
- For men: agreement to remain abstinent or use contraceptive measures and
agreement to refrain from donating sperm
Exclusion criteria
Cancer-Specific Exclusions
- Patients with a sensitizing mutation in the EGFR gene or an ALK
fusiononcogene
- Active or untreated CNS metastases as determined by computed tomography (CT)
or magnetic resonance imaging (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 tumor-related pain
- Uncontrolled or symptomatic hypercalcemia (> 1.5 millimole/Liter ionized
calcium or calcium > 12 milligram/deciliter or corrected serum calcium > upper
limit of normal)
- Malignancies other than NSCLC within 5 years prior to randomization
- Known tumor PD-L1 expression status from other clinical studies , General
Medical Exclusions:
- History of severe allergic, anaphylactic, or other hypersensitivity reactions
to chimeric or humanized antibodies or fusion proteins
- History of certain autoimmune disease
- History of idiopathic pulmonary fibrosis, organizing pneumonia, druginduced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
- Severe infections within 4 weeks prior to randomization
- 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 , Exclusion
Criteria Related to Medications and Chemotherapy:
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy
within 3 weeks prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
anti*PD-1, and anti*PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents within 4 weeks or 5
half-lives of the drug prior to randomization
- Treatment with systemic immunosuppressive medications , Exclusion Criteria
Related to Chemotherapy:
- History of allergic reactions to cisplatin, carboplatin, or other
platinum-containing compounds
- Patients with hearing impairment (cisplatin)
- Grade >= 2 peripheral neuropathy as defined by National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 criteria
(cisplatin)
- Creatinine clearance (CRCL) =< 60 milliliter (mL)/minute (min) for cisplatin
or < 45 mL/min for carboplatin
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 | EUCTR2015-003605-42-NL |
| CCMO | NL55742.100.16 |