E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SQUAMOUS NON−SMALL CELL LUNG CANCER |
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E.1.1.1 | Medical condition in easily understood language |
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 in the ITT population as measured by investigator-assessed PFS according to RECIST v1.1 in each of the following two treatment comparisons:
MPDL3280A + carboplatin + paclitaxel versus carboplatin + nab-paclitaxel
MPDL3280A + carboplatin + nab-paclitaxel versus carboplatin + nab-paclitaxel
• To evaluate the efficacy of MPDL3280A in the PD-L1−selected population as measured by investigator-assessed PFS according to RECIST v1.1 in each of the two treatment comparisons |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of MPDL3280A as measured by investigator-assessed ORR according to RECIST v1.1 in each of the two treatment comparisons
• To evaluate the efficacy of MPDL3280A as measured by OS in each of the two treatment comparisons
• To evaluate the efficacy of MPDL3280A as measured by investigator-assessed duration of response (DOR) according to RECIST v1.1 in each of the two treatment comparisons |
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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 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 EGFR-mutant 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 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 completion of chemoradiotherapy.
• Measurable disease, as defined by RECIST v1.1 |
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E.4 | Principal 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 |
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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 the disease progression as determined by the investigator using RECIST v1.1 or death from any cause, 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) as determined 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 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 |
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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 | No |
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 | 3 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
France |
Germany |
Israel |
Italy |
Japan |
Latvia |
Lithuania |
Mexico |
Netherlands |
Peru |
Portugal |
Russian Federation |
Singapore |
Slovakia |
Spain |
Sweden |
Switzerland |
Taiwan |
Ukraine |
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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |