E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
MET DIAGNOSTIC−POSITIVE NON−SMALL CELL LUNG CANCER
(NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Incurable lung cancer (NSCLC) |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025048 |
E.1.2 | Term | Lung cancer non-small cell recurrent |
E.1.2 | System Organ Class | 100000004864 |
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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 evaluate the efficacy of MetMAb compared with placebo by PFS in all patients and in the subgroup of patients with Met diagnostic–positive tumors in each of two combination treatment cohorts:
Cohort 1: MetMAb + bevacizumab + platinum + paclitaxel vs. placebo + bevacizumab + platinum + paclitaxel
Cohort 2: MetMAb + platinum + pemetrexed vs. placebo + platinum + pemetrexed
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of MetMAb compared with placebo, as measured by OS, in each treatment cohort, in all patients and in those who have Met diagnostic–positive NSCLC
• To evaluate the efficacy of MetMAb compared with placebo, as measured by overall response rate (ORR), duration of response (DOR), and disease control rate (DCR), in each treatment cohort, in all patients and in those who have Met diagnostic–positive NSCLC
• To evaluate the safety and tolerability of MetMAb compared with placebo
• To describe the pharmacokinetics (PK) of MetMAb given in combination with bevacizumab, platinum, and paclitaxel or pemetrexed
• To evaluate the possible effect of MetMAb on the PK of bevacizumab, platinum, paclitaxel, and pemetrexed
• To evaluate potential immune responses against MetMAb
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent
• Male or female, 18 years of age or older
• ECOG performance status of 0 or 1
• Stage IIIB or Stage IV NSCLC tumors of non-squamous histology (Stage IIIB eligible only if stage T4 disease not amenable to definitive surgery or radiation therapy)
• For patients who received prior adjuvant chemotherapy:
a treatment free interval of at least 12 months since the last chemotherapy cycle
• Adequate tissue for central IHC assay of Met receptor, and EGFR testing if EGFR status is unknown
• Adequate hematologic, hepatic, and renal function
• Adequate contraception, during the treatment period and for at least 90 days after the last dose of study drug/placebo or 6 months after the last dose of paclitaxel |
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E.4 | Principal exclusion criteria |
• Prior systemic treatment for Stage IIIB or IV non-squamous NSCLC
• Mixed NSCLC histology with squamous cell predominance
• Prior exposure to experimental treatment targeting either the HGF or Met pathway
• Tumors confirmed to have EGFR activating mutations suitable for anti-EGFR therapy
• Known central nervous system (CNS) disease, other than stable, treated brain metastasis
• History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years (except for in situ cancer or basal or squamous cell skin cancer)
• Serum calcium > ULN (corrected for low serum albumin concentrations)
• Uncontrolled diabetes (fasting serum glucose level > 200 mg/dL)
• Pregnancy or lactation
• Significant history of cardiovascular disease
• Serious active infection or other serious underlying medical conditions
• Known HIV positivity
• Any major surgery, major surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1, or an anticipated need for major surgery during the study
• Known sensitivity to any component of cisplatin or carboplatin
• (Patients with contraindications to bevacizumab or pemetrexed may not be included in those treatment cohorts)
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E.5 End points |
E.5.1 | Primary end point(s) |
• Progression-free survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS will be evaluated when 48 investigator-assessed PFS events in
patients with Met diagnostic-positive tumors and 96 PFS events in the ITT population have occurred. |
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E.5.2 | Secondary end point(s) |
• Overall survival (OS)
• Overall response rate (ORR)
• Duration of response (DOR)
• Disease control rate (DCR)
• Adverse events, including serious AEs
• Clinical laboratory results and vital signs
• Pharmacokinetics for all components of study treatments
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Follow-up for survival will continue until all patients have either died, or are lost to follow-up, or the Sponsor decides to end the trial, whichever occurs first. |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, QoL, Serum levels and incidence of anti-therapeutic
antibodies (ATAs) against MetMAb |
|
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
MetMAb IN COMBINATION WITH PACLITAXEL + CISPLATIN OR CARBOPLATIN |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
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 |
Argentina |
Brazil |
Colombia |
France |
Germany |
Israel |
Italy |
Latvia |
Malaysia |
Mexico |
Philippines |
Portugal |
Spain |
Taiwan |
United Kingdom |
United States |
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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
|
The efficacy analysis will occur when approx. 48 investigator-assessed PFS events in patients with Met diagnostic-positive tumors have occurred. Follow-up for survival will continue until all patients have either died, or are lost to follow-up, or the Sponsor decides to end the trial, whichever occurs first. No crossover from placebo to onartuzumab treatment will be allowed in this 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 | |
E.8.9.1 | In the Member State concerned months | 26 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 26 |
E.8.9.2 | In all countries concerned by the trial days | 0 |