A PHASE III, OPEN-LABEL, RANDOMIZED STUDY OF ATEZOLIZUMAB (MPDL3280A, ANTI-PD L1 ANTIBODY) IN COMBINATION WITH CARBOPLATIN OR CISPLATIN + PEMETREXED COMPARED WITH CARBOPLATIN OR CISPLATIN + PEMETREXED IN PATIENTS WHO ARE CHEMOTHERAPY-NAIVE AND HAVE STAGE IV NON-SQUAMOUS NON-SMALL CELL LUNG CANCER
- Conditions
- Phase 3 Non-squamous non-small cell - Lung cancer10038666
- Registration Number
- NL-OMON50326
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 59
- 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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The co-primary efficacy outcome measures for this study are:<br /><br>* PFS, defined as the time from randomization to the first occurrence of<br /><br>disease progression as determined by the investigator using RECIST v1.1 or<br /><br>death from any cause, whichever occurs first. Patients who have not experienced<br /><br>disease progression or death at the time of analysis will be censored at the<br /><br>time of last tumor assessment. Patients with no post-baseline tumor assessment<br /><br>will be censored at the randomization date plus 1 day.<br /><br>* OS, defined as the time from randomization to death from any cause</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary efficacy outcome measures for this study are:<br /><br>* Objective response, defined as PR or CR as determined by the investigator<br /><br>according to RECIST v1.1<br /><br>* DOR, defined as the time interval from first occurrence of a documented<br /><br>objective response to the time of disease progression as determined by the<br /><br>investigator using RECIST v1.1 or death from any cause, whichever comes first<br /><br>* OS at 1 and 2 year landmark timepoints<br /><br>* TTD in patient reported lung cancer symptoms, defined as time from<br /><br>randomization to deterioration (10 point change) on each of the EORTC QLQ-C30<br /><br>and EORTC QLQ-LC13 symptom subscales<br /><br>* Change from baseline in patient reported lung cancer symptoms (cough,<br /><br>dyspnea, or chest pain) with use of the SILC scale symptom score</p><br>