E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced nonsquamous non small cell lung cancer |
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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 | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
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 |
Primary Objective:
The primary objective of this study is to evaluate the overall survival (OS) in patients with Stage IV nonsquamous NSCLC treated (per the AJCC Staging Manual, Seventh Edition) with IMC-11F8 plus pemetrexed-cisplatin chemotherapy (Arm A) versus pemetrexed-cisplatin chemotherapy alone (Arm B) in the first-line metastatic setting. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
• To evaluate progression-free survival (PFS) in each arm;
• To evaluate the objective response rate (ORR) in each arm;
• To evaluate the time to treatment failure (TTF) in each arm;
• To evaluate the safety profile of IMC-11F8 in combination with pemetrexed-cisplatin chemotheray;
• To evaluate the pharmacokinetics (PK) of IMC-11F8 (Arm A only);
• To determine the immunogenicity of IMC-11F8 (Arm A only);
• To evaluate Health Status;
• To evaluate the relationship between EGFR protein expression (as measured by immunohistochemistry [IHC]) and efficacy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically- or cytologically-confirmed nonsquamous (adenocarcinoma/large cell or other) NSCLC
• Stage IV disease (per the AJCC Staging Manual, Seventh Edition) at the time of study entry.
• Measurable or nonmeasurable disease at the time of study entry as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) (patients with only truly nonmeasurable disease are not eligible).
• Archived tumor tissue available for analysis of EGFR and KRAS mutation status (by PCR) and EGFR gene copy number (by FISH); minimum of four slides, paraffin-embedded tissue, required. |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria:
• Squamous NSCLC.
• Prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the EGFR, VEGF, or VEGFR
• Previous chemotherapy for advanced NSCLC (patients who have received adjuvant chemotherapy ≥ 1 year prior to randomization are eligible)
• Major surgery or any investigational therapy in the 4 weeks prior to randomization
• Chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
• Brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants (Patients who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible.) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (defined as the time from randomization to death from any cause). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final efficacy analysis will be performed when at least 474 deaths are observed. |
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E.5.2 | Secondary end point(s) |
• Progression-free survival (PFS)
• Objective response rate (ORR)
• Time to treatment failure (TTF)
• Safety endpoints (occurrence of at least one adverse event within a subject, vital sign parameters, laboratory parameters)
• Health Status (EQ-5D Index Score and VAS-Score, LCSS Index Score)
• PK parameters
• Immunogenicity (development of antibodies against IMC-11F8)
• EGFR protein expression (as measured by immunohistochemistry) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessment for response, according to RECIST 1.0, will be performed every 6 weeks (± 3 days).
Blood for determination of serum concentrations of IMC-11F8 will be drawn prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, and 6 from patients in Arm A only.
Immunogenicity will be assessed based on serum drawn prior to the initial IMC-11F8 infusion on Day 1 of Cycles 1, 3, and 5 (Arm A only). An additional sample will be collected approximately 30 days following the last dose of IMC-11F8. Samples will also be obtained in the setting of an infusion reaction. |
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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 | 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) | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of care treatment with pemetrexed and cisplatin |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 141 |
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 |
Canada |
France |
Germany |
Greece |
India |
Italy |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
South Africa |
Spain |
United Kingdom |
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 end of the trial will be defined as the point at which no patient is receiving study therapy, all patients have completed the 30-day safety follow up evaluation subsequent to last dose, and analysis of the primary endpoint can be performed. |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |