E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-small cell lung cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
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 |
To compare the antitumor activity of LDK378 versus reference chemotherapy, as measured by PFS determined by a BIRC |
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E.2.2 | Secondary objectives of the trial |
Key secondary:
- To compare OS in patients treated with LDK378 versus reference chemotherapy
Other secondary:
1. To assess the antitumor activity of LDK378 versus reference chemotherapy, as measured by ORR, DOR, DCR, and TTR determined by BIRC and by investigators
2. To assess the antitumor activity of LDK378 versus reference chemotherapy, as measured by PFS determined by investigators
3. To assess the antitumor activity of LDK378 versus reference chemotherapy in the brain, as measured by OIRR, IDCR and DOIR as determined by BIRC neuroradiologist per modified RECIST 1.1
4. To evaluate the safety profile of LDK378 versus reference chemotherapy
5. To assess the effect of LDK378 versus reference chemotherapy on PROs, including disease related symptoms, functioning, and health-related quality of life
6. To characterize the PK of LDK378 in this patient population
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient has a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that is Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test will be performed at Novartis designated central laboratories.
2. Patient has newly diagnosed stage IIIB (who are not a candidate for definitive multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with exception of neo-adjuvant or adjuvant therapy.
3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation.
Other protocol-defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
2. Patient with a history of severe hypersensitivity reaction to platinum containing drugs, pemetrexed or any known excipients of these drugs.
3. Patient with symptomatic central nerous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.
Other protocol-defined exclusion criteria may apply
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E.5 End points |
E.5.1 | Primary end point(s) |
progression free survival (PFS), defined as time from date of randomization to date of first documented disease progression (as assessed by BIRC per RECIST 1.1) or date of death due to any cause |
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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) |
key secondary:
- overall survival (OS), defined as time from date of randomization to date of death due to any cause
other secondary:
The following endpoints will be evaluated by BIRC and by investigator assessment per RECIST 1.1:
– ORR, defined as the proportion of patients with a best overall response defined as CR or PR; (CR+PR)
– DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause
– DCR, defined as the proportion of patients with best overall response of CR, PR, or SD
– TTR, defined as the time from date of randomization to date of first documented response (CR or PR)
Other secondary endpoints as per full protocol may apply |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
for key secondary:
Month 33
for other secondary:
Month 33 |
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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 | 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 | 130 |
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 |
Australia |
Austria |
Belgium |
Brazil |
China |
Colombia |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
India |
Ireland |
Italy |
Japan |
Lebanon |
Mexico |
Netherlands |
New Zealand |
Norway |
Poland |
Russian Federation |
Singapore |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
United Kingdom |
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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 study will end once the final OS analysis is performed when approximately 253 deaths are observed or when statistical significance is reached for OS analysis (see Section 10.5.1) and the final analysis of study data will be conducted. All available OS and safety data from all patients up to this cutoff date will be analyzed. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |