E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Type of lung cancer, called non-small cell lung cancer (NSCLC) with certain genetic alterations (called mutations) of a gene called the MET gene |
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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 | 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) |
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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 |
To compare the efficacy of capmatinib versus docetaxel |
|
E.2.2 | Secondary objectives of the trial |
Key secondary objective:
To compare the Overall Response Rate (ORR) of capmatinib and
docetaxel
Other secondary objectives:
To assess the antitumor activity of capmatinib versus docetaxel
To evaluate Overall Survival (OS) in participants treated with capmatinib
versus docetaxel
To evaluate the safety profile of capmatinib versus docetaxel
To characterize the pharmacokinetics of capmatinib in this study
population
To assess the effect of capmatinib versus docetaxel on patient-reported
disease-related symptoms, functioning, and health-related quality of life
(HRQoL)
To assess intracranial anti-tumor activity of capmatinib and docetaxel in
participants with Central Nervous System (CNS) lesions at baseline by
BIRC |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained prior to participation in the study.
2. Adult ≥ 18 years old at the time of informed consent.
3. Stage IIIB/IIIC (not amenable to surgery, radiation or multi modality therapy) or IV NSCLC at the time of study entry.
4. Histologically or cytologically confirmed diagnosis of NSCLC that is:
• EGFR wt. This should have been assessed as part of the participant’s standard of care by a validated test for EGFR mutations as per local guidelines.
• AND ALK rearrangement negative. This should have been assessed as part of the participant’s standard of care by a validated test.
• AND has MET∆ex14 mutation per Novartis-designated central laboratory.
5. Mandatory provision of a formalin-fixed, paraffin embedded tumor tissue sample (archival tumor block or slides, or a newly obtained tumor sample) in a quantity sufficient to allow the confirmation of MET mutation status for all participants and potential companion diagnostics development. Tumor samples must contain at least 10% tumor content.
6. Participants must have progressed on one or two prior lines of systemic therapy for advanced/metastatic disease (stage IIIB/IIIC [not candidates for surgery, radiation or multi modality therapy] or IV NSCLC) and must be candidates for single agent chemotherapy (docetaxel).
7. ECOG performance status (PS) of 0 or 1.
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|
E.4 | Principal exclusion criteria |
1. Prior treatment with any MET inhibitor or HGF-targeting therapy.
2. Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms. If participants are on corticosteroids for endocrine deficiencies or tumor-associated symptoms other than CNS related, dose must have been stabilized (or decreasing) for at least 5 days before Cycle 1 Day 1.
3. Participants with known druggable molecular alterations (such as ROS1 translocation or BRAF mutation, etc.) which might be a candidate for alternative targeted therapies as applicable per local regulations and treatment guidelines.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) by BIRC as per RECIST 1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis and safety analyses will be performed after observing approximately 62 PFS events as assessed by BIRC. A final analysis will be performed at the end of the study. |
|
E.5.2 | Secondary end point(s) |
All calculated per RECIST 1.1, both by BIRC and investigator:
• Overall response rate (ORR)
• Duration of response (DOR)
• Time to response (TTR)
• Disease control rate (DCR)
All calculated per RECIST 1.1, by investigator:
• PFS
Overall Survival
Incidence of adverse events and serious adverse events, change in vital signs, laboratory results and ECG
Plasma concentrations and plasma PK parameters based on population PK model as appropriate.
Change from baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13, QLQ-C30, EuroQoL-5 Dimension-5 Level/EQ-5D-5L) questionnaires
Overall intracranial response rate (OIRR), duration of intracranial response (DOIR), time to intracranial response (TTIR), intracranial disease control rate (IDCR) by BIRC as per RANO-BM criteria
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The primary analysis and safety analyses will be performed after observing approximately 62 PFS events as assessed by BIRC. A final analysis will be performed at the end of 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 | 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 | Yes |
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
| 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 | 49 |
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 |
Brazil |
India |
Israel |
Korea, Republic of |
Russian Federation |
South Africa |
Belgium |
France |
Germany |
Hungary |
Italy |
Lithuania |
Portugal |
Netherlands |
Spain |
|
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
|
|
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 | 5 |
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 | 5 |