E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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 | 18.0 |
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 | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) Phase Ib: To estimate the MTD or RP2D of INC280 in combination with gefitinib in NSCLC patients who have c-MET gene dysregulation
2) Phase II: To estimate overall clinical activity of INC280 in combination with gefitinib in NSCLC patients with c-MET gene dysregulation |
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E.2.2 | Secondary objectives of the trial |
1) To determine safety and tolerability of INC280 in combination with gefitinib
2) To estimate time dependent clinical activity of INC280 in combination with gefitinib
3) To assess the pharmacodynamic effect of INC280 in combination with gefitinib
4) To characterize the PK profile of INC280 and gefitinib in NSCLC patient population and to assess potential drug interaction between INC280 and gefitinib |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Confirmed c-MET pathway dysregulation
- EGFR mutated NSCLC patient who have developed acquired resistance to EGFR inhibitor treatment
- Measurable disease as determined by RECIST version 1.1
-ECOG performance status ≤2
- Documented c-Met amplification
- Prior clinical benefit on EGFR inhibitors and then subsequent progression
- ≥ 18 years of age
- Life expectancy ≥3 months
Other protocol inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
- Previous treatment with a c-MET inhibitor or HGF-targeting therapy
- Previous radiation therapy completed less than 4 weeks prior to dosing and, if present, any acute toxicity > grade 1
- history of cystic fibrosis
- history of acute or chronic pancreatitis, surgery of the pancreas, or any risk factors that may increase the risk of pancreatitis.
- Unable to swallow tablets once or twice daily
- Any unresolved toxicity from previous anticancer therapy greater than Grade 1 except alopecia.
- Unable to undergo an MRI or CT procedures
- Known history of HIV
- Undergone a bone marrow or solid organ transplant
- Pregnant or nursing
Other protocol exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Phase Ib : Frequency and characteristics of dose limitting toxicities (DLTs)
2) Phase II : Overall Response Rate of tumors per RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) From date of treatment until DLT, up to 52 weeks
2) From date of treatment until disease progression, up to 100 weeks |
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E.5.2 | Secondary end point(s) |
1) Overall Survival (OS)
2) Frequency, duration and severity of adverse events (AEs)
3) Inhibition of c-MET signaling by pre- and post-treatment immunohistochemistry of p-MET
4) Plasma concentration of INC280
5) Progression Free Survival (PFS)
6) Plasma concentration of gefitinib
7) PK parameter AUC
8) PK parameter Cmax
9) PK parameter Tmax
10) PK parameter accumulation ratio
11) PK parameter half-life
12) number of SAEs, and severity of SAEs
13) number of AEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) From date of treatment until death, up to 5 years
2) 30 days post study treatment
3) Day 15 of cycle 1
4) Day 1 of cycle 4
5) From date of treatment to the date of disease progression, up to 5 years
6, 7, 8, 9, 10, 11) Day 1 and 15 cycle 2, Day 1 of cycle 3 and 4
12 and 13) 30 days post study treatment
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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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
dose escalation in combination with gefitinib |
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 19 |
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 |
Belgium |
China |
Czech Republic |
Denmark |
France |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
New Zealand |
Norway |
Singapore |
Spain |
Switzerland |
Taiwan |
Thailand |
United Kingdom |
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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
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upon completion of the follow-up period for all patients treated with study treatment |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |