E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PD-L1-POSITIVE LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER |
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E.1.1.1 | Medical condition in easily understood language |
PD-L1-POSITIVE LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The primary efficacy objective for this study is to evaluate the efficacy of MPDL3280A in patients with PD-L1−positive locally advanced or metastatic NSCLC, as measured by investigator-assessed ORR according to modified RECIST |
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E.2.2 | Secondary objectives of the trial |
- To evaluate PFS and DOR according to modified RECIST
- To evaluate the efficacy of MPDL3280A in patients with PD-L1-positive locally advanced or metastatic NSCLC, as measured by investigator-assessed ORR, DOR, PFS, where all response endpoints are determined according to RECIST 1.1
- To evaluate OS
- To evaluate PFS in patients who experience a confirmed partial response (PR) or confirmed CR per modified RECIST at any time on study treatment
- To evaluate the safety and tolerability of MPDL3280A in patients with PD-L1-positive locally advanced or metastatic NSCLC
- To characterize the pharmacokinetics of MPDL3280A
- To evaluate the incidence and titers of ATAs against MPDL3280A and to explore the potential relationship of the immunogenicity response with pharmacokinetics, safety, and efficacy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically or cytologically documented Stage IIIB (not eligible for definitive chemoradiotherapy), Stage IV, or recurrent NSCLC
- PD-L1−positive status as determined by an IHC assay performed by a central laboratory
- ECOG performance status of 0 or 1
- Measurable disease, as defined by RECIST v1.1
Inclusion Criteria Unique to Cohort 1:
- No prior chemotherapy for locally advanced or metastatic (i.e., Stage IIIB not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) NSCLC
Inclusion Criteria Unique to Cohorts 2 and 3
- Disease progression during or following prior platinum-based chemotherapy for locally advanced or metastatic (i.e., Stage IIIB not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) NSCLC
Inclusion Criteria Unique to Cohort 3
- Diagnosis of brain metastases by brain MRI or contrast-enhanced CT |
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E.4 | Principal exclusion criteria |
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
- Known CNS disease, including treated brain metastases: Cohorts 1 and 2
- Leptomeningeal disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
investigator overall response rate (ORR) per modified RECIST |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
timepoint for evaluation will be 6 months after approximately 130 patients have been enrolled; |
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E.5.2 | Secondary end point(s) |
ORR, duration of response (DOR), progression-free survival (PFS), and overall survival (OS) per RECIST v1.1, |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
timepoint for evaluation is same as for primary endpoint, with updated analysis approximately 12 months after the last patient is enrolled in the study |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
France |
Germany |
Italy |
Netherlands |
Spain |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of study is defined as the date of the last follow-up visit of the last patient enrolled and is expected to occur approximately 12 months after the last patient enters the re-treatment stage. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |