E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with ALK-positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
metastatic or locally advanced 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 | 17.0 |
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) |
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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 objective of the study is to determine the efficacy of AP26113, as evidenced by objective response rate, in patients with ALK-positive locally advanced or metastatic NSCLC whose disease has progressed on therapy with crizotinib. Two dosing regimens will be tested. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study (for each dosing regimen) are: 1. To further characterize the efficacy of AP26113 in patients with ALK-positive, locally advanced or metastatic NSCLC whose disease has progressed on therapy with crizotinib, as shown by disease control rate, time to/duration of response, progression-free survival (PFS), overall survival (OS), and time on treatment. 2. To assess CNS response and PFS, per RECIST v1.1, in those patients who have active brain metastases. 3. To assess the safety and tolerability of AP26113 in study patients. 4. To measure steady-state plasma levels of AP26113 for use in population PK modeling. 5. To assess patient-reported symptoms and health-related quality of life (HRQoL) with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 (v3.0).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients must meet all the following eligibility criteria for study entry: 1. Have histologically or cytologically confirmed locally advanced or metastatic NSCLC that is ALK+. 2. Must meet one of the following two criteria: a. Have documented ALK rearrangement by a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or b. Have documented ALK positivity by a different test and tissue available for the Vysis® FISH test. Tissue should be derived preferably from abiopsy taken after progression with crizotinib. If such a sample is not available, testing may be performed with archived tumor tissue. 3. Had progressive disease while on crizotinib, as assessed by the investigator or treating physician. 4. Received crizotinib as the last therapy, within 30 days of the first dose of AP26113. This criterion may be met by reintroduction of crizotinib after intervening therapy. If crizotinib was reintroduced, documented progression on the most recent regimen of crizotinib must have occurred. 8. Are a male or female patient ≥18 years old. |
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E.4 | Principal exclusion criteria |
Patients meeting any of the criteria below are ineligible for the study: 1. Received any prior ALK-targeted TKI other than crizotinib. 2. Received crizotinib within 3 days of the first dose of AP26113 (Day 1, Cycle1). 3. Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery. 4. Received monoclonal antibodies or had major surgery within 30 days of the first dose of AP26113 (Day 1, Cycle 1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint: Confirmed Objective Response Rate (ORR), as assessed by the investigator, per RECIST v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 8 weeks (from Day 1 of Cycle 3 through Cycle 15; every 3 cycles thereafter) |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints: 1. Confirmed ORR, as assessed by a central independent review committee (IRC), per RECIST v1.1 2. CNS response (ORR and PFS, per RECIST v1.1, in patients who have active brain metastases) 3. Time to response 4. Duration of response 5. Time on treatment 6. Disease control rate (the percentage of patients with best response of complete response [CR], PR, or SD), per RECIST v1.1 7. Progression Free Survival (PFS) 8. Overall Survival (OS) 9. Safety and tolerability 10. Steady-state plasma level of AP26113 for use in population PK modeling 11. Patient-reported symptoms of lung cancer and HRQoL scores, assessed with the EORTC QLQ-C30 (v3.0) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Collection of secondary endpoints will continue for 2 years after the last patient enrolls into 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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Canada |
Hong Kong |
Korea, Republic of |
Singapore |
Switzerland |
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 trial will end when all patients have discontinued from the trial, but no longer than 2 years after the last patient enrolls into the study. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |