E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced/Recurrent Non Squamous 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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10029664 |
E.1.2 | Term | Non-small cell neoplasms malignant of the respiratory tract cell type specified |
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 demonstrate the efficacy equivalence of FKB238 and EU-Avastin when used in combination with paclitaxel/carboplatin as measured by ORR |
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E.2.2 | Secondary objectives of the trial |
To compare FKB238 and EU-Avastin through:
- Overall response rate at week 19
- Progression-free Survival
- Overall Survival
- Duration Of Response
- Disease Control Rate
To compare the safety of FKB238 and EU-Avastin
To compare the ADAs produced by FKB238 and EU-Avastin
To compare the serum trough concentration (Ctrough) of FKB238 and EU-Avastin
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients aged 18 years or older
• Newly diagnosed advanced (stage IV) /recurrent non-squamous NSCLC for which they had not received any systemic anti-cancer therapy for metastatic disease
• Histologically or cytologically confirmed diagnosis of predominantly non-squamous NSCLC
• Existence of at least 1 measurable lesion by response evaluation criteria
• Adequate haematological, renal and liver function
Other inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
• Small cell lung cancer (SCLC) or combination SCLC and NSCLC. Squamous-cell tumours and mixed adenosquamous carcinomas of predominantly squamous nature
• Any unresolved toxicities from prior systemic therapy
• Known sensitising EGFR mutations or EML4-ALK translocation positive mutations
• Previous dosing with vascular endothelial growth factor (VEGF) inhibitor
• Known hypersensitivity to active ingredients or any excipients of the IPs and combination chemotherapy
• Use of prohibited concomitant medication
• Known Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection
• Fertile men or women of childbearing potential not using adequate contraception
Other exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate (by Response Evaluation Criteria [RECIST] v1.1) assessed as the rate of the best response (complete response [CR] or partial response [PR]) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomisation to study treatment discontinuation |
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E.5.2 | Secondary end point(s) |
•Overall response rate (ORR) (by RECIST v1.1) at week 19, defined as
the rate of the best response of Complete Response (CR) or Partial
Response (PR) assessed at week 19
•Progression-free Survival (PFS), defined as the time from randomisation to the first documented disease progression (PD) or death, whichever occurs first
• Overall Survival (OS), defined as the time from randomisation to death from any cause
• Duration Of Response (DOR), defined as the time from the first documented Partial Response (PR) or Complete Response (CR) (by RECIST v1.1) to the first documented objective PD or death, whichever occurs first
• Disease Control Rate (DCR), defined as the rate of CR, PR, Stable Disease (SD) (≥6 weeks)
• Safety as evaluated through Adverse Events (AEs), vital signs, haematology, clinical chemistry, urinalysis, electrocardiogram (ECG), Eastern Collaborative Oncology Group Performance Status (ECOG PS), and physical examination
• Immunogenicity (presence of ADAs)
• Pharmacokinetics (PK) (Ctrough)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• PFS: from randomisation to the first documented disease progression (PD), death or data cut-off, whichever occurs first
• OS: from randomisation to death from any cause or data cut-off
• DOR: from the first documented Partial Response (PR) or Complete Response (CR) (by RECIST v1.1) to the first documented objective PD or death, whichever occurs first
• DCR: the rate of CR, PR, Stable Disease (SD) (≥6 weeks)
• Safety: from signature of informed consent, up to and including 30-day follow-up after last dose of study treatment
• Immunogenicity: from randomisation to the end of follow-up period, death, lost to follow-up or data cut-off, whichever occurs first
• PK: from randomisation to the end of follow-up period, death, lost to follow-up or data cut-off, 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 | 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 | 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) | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Belarus |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Canada |
Croatia |
France |
Georgia |
Germany |
Greece |
Hungary |
Italy |
Japan |
Korea, Republic of |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
Serbia |
Spain |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
Vietnam |
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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 study is defined as the last patient last visit. The
endpoint analyses occur after data cut-off, which is a minimum of 12
months after randomisation of the last patient enrolled. The Extended
Treatment Period is the time after data cut-off to end of study in which
patients may continue receiving IP if they are considered to be gaining
clinical benefit. These patients may receive treatment until withdrawal,
PD, or death. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |