E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The intended use of SB8 is the treatment of metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
The intended use of SB8 is the treatment of metastatic or recurrent non-squamous non-small cell 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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029514 |
E.1.2 | Term | Non-small cell lung cancer NOS |
E.1.2 | System Organ Class | 100000015833 |
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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 equivalence of SB8 to Avastin®, in terms of the best overall response rate (ORR) by 24 weeks of chemotherapy in subjects with metastatic or recurrent non squamous NSCLC. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of SB8 compared to Avastin® by
- Progression free survival (PFS)
- Overall survival (OS)
- Duration of response (DOR)
• To evaluate the safety and tolerability of SB8 compared to Avastin®
• To evaluate the pharmacokinetics of SB8 compared to Avastin®
• To evaluate the immunogenicity of SB8 compared to Avastin®
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Approximately 50% of the enrolled subjects will be participating by default in the PK sub-study for PK assessment and those subjects will be defined at the time of randomisation in the IWRS. PK assessments will be performed to provide supportive evidence to PK similarity. |
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E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria to be eligible for the study:
1. Aged ≥ 18 years (if local regulations are different in this regard, follow the local regulations).
2. ECOG performance status of 0-1 at Screening.
3. Histologically and/or cytologically confirmed metastatic (AJCC 7th edition TNM stage IV) or recurrent non-squamous NSCLC or NSCLC-not otherwise specified (NOS).
4. At least one measurable lesion according to RECIST v1.1.
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria are not eligible for the study:
1. Diagnosis of small cell carcinoma of the lung or squamous cell carcinoma of the lung. For mixed tumour with the component of squamous cell carcinoma, it should be categorised according to predominant histology. Any component of small cell carcinoma of the lung is to be excluded.
2. Known activating mutations in EGFR gene or transforming rearrangements of ALK gene.
3. Radiological or clinical evidence of tumour invasion into blood vessels or close to large vessels that may have risk of bleeding at the discretion of Investigator.
4. History of systemic anti-cancer therapy administered in the first-line setting for metastatic or recurrent disease of NSCLC.
5. Any systemic anti-cancer therapy including neoadjuvant or adjuvant chemotherapy administered for NSCLC and completed less than 12 months prior to Randomisation.
6. Previously treated with a monoclonal antibody and/or molecule targeting VEGFR-related and/or EGFR-related signalling pathways.
7. Radiotherapy within 14 days prior to Randomisation (tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy are not considered as measurable lesion unless there has been demonstrated progression in the lesion.).
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E.5 End points |
E.5.1 | Primary end point(s) |
•The best ORR by 24 weeks of chemotherapy (best ORR is defined as the proportion of subjects whose best overall response is either complete response [CR] or partial response [PR] according to RECIST v1.1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumour assessment will be performed after IP administration of Cycle 2, 4, and 6, and before planned Day 1 of Cycle 3, 5, and 7 and then will be performed every 4 cycles according to RECIST v1.1 and tumour size will be assessed by both Investigators and independent central reviewer. |
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E.5.2 | Secondary end point(s) |
• Progression free survival (PFS)
• Overall survival (OS)
• Duration of response (DOR) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Progression free survival (PFS), defined as the time from the date of Randomisation to the date of disease progression or death regardless of the cause of death. Subjects who are not progressed at the time of analysis will be censored at the date of EOT visit or the last tumour assessment date if the date of EOT is not available.
• Overall survival (OS), defined as the time from the date of Randomisation to the date of death regardless of the cause of death. Subjects who are alive at the time of analysis will be censored at the date of last known alive.
• Duration of response (DOR), defined as the time from documented tumour response (complete or partial) until documented disease progression. Only the subjects who achieve an initial tumour response will be evaluated for DOR. |
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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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 |
Belarus |
Georgia |
Germany |
Hungary |
Korea, Republic of |
Poland |
Romania |
Russian Federation |
Serbia |
Spain |
Taiwan |
Ukraine |
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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 date when deaths of all the randomised subjects have been observed, or 12 months from Randomisation of the last subject, whichever occurs first. |
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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 | 6 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |