E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Non-squamous Non-Small Cell Lung Cancer (NSCLC) |
Rozvinutá neskvamózna nemalobunková rakovina pľúc (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
lung cancer on late stages |
rakovina pľúc v pokročilom štádiu |
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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 | 10079440 |
E.1.2 | Term | Non-squamous non-small cell lung cancer |
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 and compare efficacy of BCD-100 in combination with pemetrexed+cisplatin/carboplatin and Placebo in combination with pemetrexed+cisplatin/carboplatin as first-line treatment in subjects with metastatic NSCLC using OS |
Zhodnotiť a porovnať účinnosť BCD-100 v kombinácii s pemetrexed+cisplatina/karboplatina a Placeba v kombinácii s pemetrexed+cisplatina/karboplatina ako prvej línie liečby u pacientov s metastatickou NSCLC s použitím OS |
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E.2.2 | Secondary objectives of the trial |
• To evaluate and compare efficacy of BCD-100 in combination with pemetrexed+cisplatin/carboplatin and Placebo in combination with pemetrexed+cisplatin/carboplatin as first-line treatment in subjects with metastatic NSCLC using ORR and PFS per RECIST 1.1 as assesses by BICR; • To evaluate efficacy of BCD-100 in combination with pemetrexed+cisplatin/carboplatin versus Placebo in combination with pemetrexed+cisplatin/carboplatin according to PD-L1 expression status using OS, PFS, ORR, DCR • To evaluate and compare the safety of BCD-100 in combination with pemetrexed+cisplatin/carboplatin and Placebo in combination with pemetrexed+cisplatin/carboplatin as first-line treatment in subjects with metastatic NSCLC
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• Zhodnotiť a porovnať účinnosť BCD-100 v kombinácii s pemetrexed + cisplatina/karboplatina a Placeba v kombinácii s pemetrexed + cisplatina/karboplatina ako prvej línie liečby u pacientov s metastatickou NSCLC s použitím ORR a PFS na základe RECIST 1.1 podľa hodnotenia BICR; • Zhodnotiť účinnosť BCD-100 v kombinácii s pemetrexed + cisplatina/karboplatina versus Placebo v kombinácii s pemetrexed + cisplatina/karboplatina podľa stavu expresie PD-L1 s použitím OS, PFS, ORR, DCR; • Zhodnotiť a porovnať bezpečnosť BCD-100 v kombinácii s pemetrexed+ cisplatina/karboplatina a Placeba v kombinácii s pemetrexed+cisplatina/ karboplatina ako prvej línie liečby u pacientov s metastatickou NSCLC.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
3. Previously untreated subjects with histologically-confirmed stage IV (M1a/M1b/M1c- AJCC 8th edition) non-squamous NSCLC; 5. The time from the completion of previous adjuvant/neoadjuvant treatment to metastatic disease development is no less than 12 months 6. Has a life expectancy of at least 12 weeks; 7. Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; 9. Agreement to newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for determination of PD-L1 status prior to randomization (if obtaining of new sample is contraindicated or puts subject at unacceptable risks, then fresh archival tumor tissue sample must be available) 10. Measurable disease according to CT/MRI scan (RECIST 1.1 criteria), confirmed by the local assessment
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3. Predtým neliečení pacienti s histologicky potvrdenou neskvamóznou NSCLC, štádium IV (M1a/M1b/M1c- AJCC 8. vydanie) 5. Čas od ukončenia predchádzajúcej adjuvantnej/neoadjuvantnej liečby do rozvoja metastatického ochorenia nie je kratší ako 12 mesiacov; 6. Predpokladaná dĺžka života aspoň 12 týždňov; 7. Má ECOG (Eastern Cooperative Oncology Group) Performance status 0 alebo 1; 9. Súhlas s novo získanou jadrovou alebo excíznou biopsiou nádorovej lézie, ktorá nebola predtým ožiarená na stanovenie statusu PD-L1 pred randomizáciou (ak je získanie novej vzorky kontraindikované alebo vystavuje subjekt neprijateľným rizikám, musí byť k dispozícii archívna vzorka nádorového tkaniva) 10. Merateľné ochorenie podľa CT skenovania (kritériá RECIST 1.1) potvrdené lokálnym posúdením; |
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E.4 | Principal exclusion criteria |
1. Has predominantly squamous cell histology NSCLC; Mixed tumours will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible. 2. Presence of EGFR mutation or ALK rearrangement; 3. Has received prior systemic cytotoxic chemotherapy/chemoradiotherapy for metastatic disease; 4. Has received antineoplastic therapy with targeted or immunotherapeutic drugs (including but not limited to EGFR inhibitors [e.g., erlotinib, gefitinib, cetuximab], ALK inhibitors, PD-1/PD-L1/PD-L2/CTLA4, VEGF/VEGFR inhibitors) or it is expected to require any other form of antineoplastic therapy while on study; 11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; 12. Active or known or suspected autoimmune disease (subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll). |
1. Prevažne skvamózna bunková histológia NSCLC. Zmiešané nádory budú kategorizované prevládajúcim bunkovým typom; ak sú prítomné malé bunkové prvky, subjekt je nevhodný. 2. Prítomnosť EGFR mutácie alebo ALK translokácie; 3. Predchádzajúca systémová cytotoxická chemoterapia/chemoradiačná terapia pre metastatické ochorenie; 4. Predchádzajúca antineoplastická liečba s cielenými alebo imunoterapeutickými liekmi (vrátane, ale nie iba EGFR inhibítormi [napr. erlotinib, gefitinib, cetuximab], ALK inhibítormi, PD-1/PD-L1/PD-L2/CTLA4, VEGF/VEGFR inhibítory) alebo sa očakáva, že počas skúšania bude potrebná akákoľvek iná forma protinádorovej terapie; 11. Známe aktívne metastázy centrálneho nervového systému (CNS) a/alebo karcinomatóznu meningitídu; 12. Subjekty s aktívnym alebo známym alebo domnelým autoimunitným ochorením (diabetes mellitus typu 1, hypotyreózou vyžadujúcou iba hormonálnu náhradu, alebo s kožnými ochoreniami ( vitiligo, psoriáza alebo alopécia) nevyžadujúcimi systémovú liečbu), sa môžu zaradiť do skúšania.
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E.5 End points |
E.5.1 | Primary end point(s) |
overall survival (OS) - the time from the date of randomization until death due to any cause |
Celkové prežitie (OS) - od začiatku randomizácie až po smrť v dôsledku akejkoľvek príčiny |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
OS will be assessed according to the data obtained at regular visits and during the follow-up by phone up to 3 years from the start of the therapy or until the end of the study |
OS sa bude hodnotiť podľa údajov získaných pri pravidelných návštevách a počas sledovania telefonickými hovormi až do 3 rokov od začiatku liečby alebo do konca klinického skúšania. |
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E.5.2 | Secondary end point(s) |
• progression-free survival (PFS) per RECIST 1.1 criteria assessed by BICR - the time from the date of randomization until progression of disease according to RECIST 1.1 criteria or death, • overall response rate (ORR) per RECIST 1.1 criteria assessed by BICR, • disease control rate (DCR) per RECIST 1.1 criteria assessed by BICR, • time to response (TTR), • duration of response (DOR)
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• Prežitie bez progresie (PFS) – podľa kritéria RECIST 1.1 stanoveného BICR - trvanie od randomizácie až po progresiu ochorenia alebo smrť, • Celková miera odpovede (ORR) - podľa kritéria RECIST 1.1 stanoveného BICR, • Miera kontroly ochorenia (DCR) - podľa kritéria RECIST 1.1 stanoveného BICR, • Čas na odpoveď (TTR), • Dĺžka trvania odpovede (DOR).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS, ORR, DCR, TTR, DOR will be assessed based on results of CT/MRI according to RECIST 1.1 criteria by blinded independent central review (BICR). Additional assessment of PFS and ORR will be performed according to iRECIST criteria. Contrast-enhanced CT/MRI will be performed on weeks 7, 13, 19, 25, 31, 40, 49, 61, 73, 97, 121, 145, additional CT/MRI scans can be performed within unscheduled visits. |
PFS, ORR, DCR, TTR, DOR budú hodnotené na základe výsledkov CT/MRI podľa RECIST 1.1 kritérií zaslepeným, centrálnym, nezávislým hodnotením (BICR). Dodatočné hodnotenie PFS a ORR bude vykonané podľa kritéria iRECIST. CT/MRI s kontrastnou látkou bude vykonané v týždňoch 7, 13, 19, 25, 31, 40, 49, 61, 73, 97, 121, 145, dodatočné CT/MRI môžu byť vykonané v rámci neplánovaných návštev |
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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 |
Immunogenicity |
Imunogenicita |
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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) | No |
E.8.2.2 | Placebo | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
China |
Czechia |
Hungary |
Romania |
Russian Federation |
Slovakia |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |