E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with locally advanced or metastatic (stage IIIb-IVb) EGFRm (exon 19 deletion or exon 21 L858R) NSCLC with T790M resistance mutation at progression on prior EGFR TKI therapy |
|
E.1.1.1 | Medical condition in easily understood language |
Patients who already received EGFR Inhibitor therapy against their lung cancer that has progressed or spread to other parts of the body and that has specific changes in the EGFR gene |
|
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
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) |
|
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 assess the efficacy of the combination of osimertinib and bevacizumab versus osimertinib alone in terms of progression-free survival (PFS) assessed by RECIST 1.1. |
|
E.2.2 | Secondary objectives of the trial |
To compare short and long term clinical efficacy outcomes as well as tolerability of the two treatments. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• NSCLC, stage IIIb/IIIc (not amenable to radical therapy) or IVa/IVb according to 8th TNM classification, after progression following prior EGFR TKI (erlotinib, gefitinib, dacomitinib or afatinib) therapy as the most recent treatment regimen. • Pathological diagnosis of predominantly non-squamous NSCLC. • Maximum of one line of previous platinum based chemotherapy. • Histological or cytological confirmation of EGFRm (exon19 deletion or exon 21 L858R). • Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating tumour DNA, documented in tissue, plasma or serum after disease progression on the most recent EGFR TKI regimen. • Plasma, serum, and tumour (preferred) tissue or cytology (if biopsy was taken and FFPE tumor material is not yet fully depleted) after disease progression on the most recent EGFR TKI treatment available for central confirmation of T790M. • Measurable or evaluable disease • Adequate haematological, renal and liver function • Performance status 0-2
|
|
E.4 | Principal exclusion criteria |
• Patients with mixed NSCLC with predominantly squamous cell cancer, or with any small cell lung cancer (SCLC) component. • Symptomatic or active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. • Previous treatment with osimertinib and/or bevacizumab • Patients currently receiving medications or herbal supplements known to be potent CYP3A4 inducers • Any unresolved toxicities from prior therapy greater than CTCAE V 4.0 grade 1
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) based on RECIST 1.1 criteria |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time from the date of randomisation until documented progression or death, if progression is not documented |
|
E.5.2 | Secondary end point(s) |
• Objective Response (OR), based on RECIST 1.1 criteria • Disease control, defined as complete or partial response, or disease stabilisation, confirmed at subsequent radiological assessment •Adverse events graded by CTCAE V4.0 •Overall survival (OS)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• OR : across all assessment time-points during the period from randomisation to termination of trial Treatment • Disease control: across all assessment time-points during the period from randomisation to termination of trial Treatment • AEs:from date of signature of informed consent until 30 days after all Trial Treatment discontinuation • OS: time from the date of randomisation until death from any cause |
|
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 | No |
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) | 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 | 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 | Yes |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Korea, Republic of |
Singapore |
Switzerland |
Netherlands |
Spain |
|
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
|
The required total trial follow-up duration is expected to be 48 months. Estimating a run-in period of 6 months, and a 6-month preparation of the report, the total trial duration is expected to be 5 years from enrolement of the first Patient.
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |