E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
STAGE IV NON-SQUAMOUS NON−SMALL CELL LUNG CANCER |
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E.1.1.1 | Medical condition in easily understood language |
STAGE IV NON-SQUAMOUS NON−SMALL CELL LUNG CANCER |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate the efficacy of MPDL3280A+ carboplatin + nab-paclitaxel compared withcarbopatin+ nab-paclitaxel in the ITT population as measured byinvestigator−assessed PFS according to RECIST v1.1
•To evaluate the efficacy of MPDL3280A+ carboplatin + nab-paclitaxel compared withcarbopatin+ nab-paclitaxel in the PD-L1−selected population as measured by investigator-assessed PFS according to RECIST v1.1 |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of MPDL3280A+ carboplatin + nab-paclitaxel compared withcarbopatin+ nab-paclitaxel as measured by investigator-assessed ORR according toRECIST v1.1 for both the ITT and PD-L1−selected populations
•To evaluate the efficacy of MPDL3280A+ carboplatin + nab-paclitaxel compared withcarbopatin+ nab-paclitaxel as measured by OS for both the ITT and PD-L1−selectedpopulations
•To evaluate the efficacy of MPDL3280A+ carboplatin + nab-paclitaxel compared withcarbopatin+ nab-paclitaxel as measured by investigator-assessed duration ofresponse (DOR) according to RECIST v1.1 for both the ITT and PD-L1−selected populations |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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 EGFR-mutant NSCLC. Patients not previously tested for mutational status and who have not been previously treated with an EGFR TKI will be required to be tested at screening.
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 not previously tested for ALK status and who have not previously been treated with an ALK inhibitor will be requred to be tested at screening.
• Patients who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy or chemoradiotherapy cycle.
•Measurable disease, as defined by RECIST v1.1
•Known PD-L1 tumor status as determined by an IHC assay performed by a centrallaboratory on previously obtained archival tumor tissue or tissue obtained from abiopsy at screening |
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E.4 | Principal exclusion criteria |
•Active or untreated CNS metastases as determined by CT or MRI evaluation duringscreening and prior radiographic assessments
•Spinal cord compression not definitively treated with surgery and/or radiation orpreviously diagnosed and treated spinal cord compression without evidence thatdisease has been clinically stable for > 2 weeks prior to randomization
•Leptomeningeal disease
•Uncontrolled tumor-related pain
Patients requiring pain medication must be on a stable regimen at study entry.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to randomization.
•Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrentdrainage procedures (once monthly or more frequently)
•Malignancies other than NSCLC within 5 years prior to randomization, with theexception of those with a negligible risk of metastasis or death (e.g., expected5-year OS> 90%) treated with expected curative outcome (such as adequatelytreated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localizedprostate cancer treated surgically with curative intent, ductal carcinoma in situtreated surgically with curative intent)
•Known tumor PD-L1 expression status from other clinical trials (e.g., patients whosePD-L1 expression status was determined during screening for entry into a trial withanti-programmed death-1 [PD-1] or anti-PD-L1 antibodies but were not eligible areexcluded)
•History of severe allergic, anaphylactic, or other hypersensitivity reactionsto chimeric or humanized antibodies or fusion proteins
•Positive test for HIV |
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E.5 End points |
E.5.1 | Primary end point(s) |
•PFS, defined as the time from randomization to the first occurrence of diseaseprogression as determined by the investigator using RECIST v1.1 or death from anycause, whichever occurs first |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Objective response, defined as partial response (PR) or complete response (CR) asdetermined by the investigator according to RECIST v1.1
•OS, defined as the time from randomization to death from any cause
•DOR, defined as the time interval from first occurrence of a documented objectiveresponse to the time of disease progression as determined by the |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Germany |
Israel |
Italy |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is when the required number of deaths have been observed |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |