E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer |
Cancro del polmone non a piccole cellule |
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E.1.1.1 | Medical condition in easily understood language |
Non-Small Cell Lung Cancer |
Cancro del polmone non a piccole cellule |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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 |
The primary objective is to determine the overall response rate (ORR) of telisotuzumab vedotin in subjects with c-Met+ NSCLC. |
L’obiettivo primario è quello di determinare il tasso di risposta globale (overall response rate, ORR) per telisotuzumab vedotin in soggetti con NSCLC c-Met+. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to determine Duration of response (DoR), Disease control rate (DCR), Duration of disease control (DDC), Progression Free Survival (PFS), Overall Survival (OS), Safety and Tolerability. |
Gli obiettivi secondari intendono determinare la Durata della risposta (duration of response, DoR), il Tasso di controllo della malattia (disease control rate, DCR), la Durata del controllo della malattia (duration of disease control, DDC), la Sopravvivenza libera da progressione (Progression Free Survival, PFS), la Sopravvivenza globale (Overall Survival, OS), la Sicurezza e tollerabilità |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed non-small cell lung cancer (NSCLC) with known epidermal growth factor receptor (EGFR) status (wild type or mutant; with site documented status), or histologically documented squamous cell NSCLC. • Has locally advanced or metastatic NSCLC. • Has c-Met+ NSCLC as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory. • If a subject meets eligibility criteria for c-Met protein expression level based on archival tissue material, subject must agree to submit fresh tumor material for assessment of c-Met protein expression level prior to first dose of telisotuzumab vedotin • Subjects who have progressed on systemic cytotoxic chemotherapy (or ineligible) and an immune checkpoint inhibitor (as monotherapy or in combination with systemic cytotoxic chemotherapy, or ineligible), and prior anti-cancer therapies targeting driver gene alterations (if applicable). • Subject must have received no more than 2 lines of prior systemic therapy (including no more than 1 line of prior systemic cytotoxic chemotherapy) in the metastatic setting. • Subjects should not have received prior cMET-targeted antibody-based therapies. • Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. |
• Soggetto con conferma istologica di carcinoma polmonare non a piccole cellule (NSCLC) di cui sia conosciuto lo status relativo al recettore del fattore di crescita dell’epidermide (EGFR) (wild type oppure mutante; secondo determinazione eseguita presso il centro), oppure con conferma istologica di NSCLC squamocellulare • Soggetti con NSCLC localmente avanzato oppure metastatico • Soggetto affetto da NSCLC c-Met+ in base alla valutazione di un laboratorio immunoistochimico (IHC) designato da AbbVie. • Qualora un soggetto soddisfi i criteri di eleggibilità relativi al livello di espressione della proteina c-Met in base al campione di tessuto conservato, il soggetto dovrà acconsentire a fornire un campione di tessuto tumorale ottenuto da nuova biopsia per la valutazione dei livelli di espressione della proteina c-Met prima di ricevere la prima dose di telisotuzumab vedotin. • Soggetto che ha presentato progressione in corso di chemioterapia citotossica sistemica (o che sia non idoneo a tale terapia) e con un inibitore del checkpoint immunitario (in monoterapia oppure in combinazione con chemioterapia citotossica sistemica, oppure che sia non idoneo a tale terapia), e pregresse terapie antineoplastiche mirate alle anomalie di gene driver (se applicabile). • Il soggetto deve aver ricevuto non più di 2 linee di terapia sistemica pregressa (compresa non più di 1 linea di chemioterapia citotossica sistemica pregressa) per malattia metastatica. • I soggetti non devono aver ricevuto terapie pregresse a base di anticorpi anti-c-MET. • Soggetto con punteggio ECOG (Eastern Cooperative Oncology Group) 0 -1. |
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E.4 | Principal exclusion criteria |
• Has adenosquamous histology. • Has received anti-cancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy as described in the protocol. • Has known uncontrolled metastases to the central nervous system (CNS). Subjects with brain metastases are eligible if they meet requirements described in the protocol. • Has a clinically significant condition(s) described in the protocol. • Has unresolved clinically significant adverse events >= grade 2 from prior anticancer therapy, except for alopecia or anemia. • Had major surgery within 21 days prior to the first dose of telisotuzumab vedotin. • Subject must not have a history of interstitial lung disease or pneumonitis that required treatment with systemic steroids. |
• Soggetto con evidenza istologica di carcinoma adenosquamoso. • Soggetto che ha ricevuto terapia antineoplastica fra cui chemioterapia, radioterapia, immunoterapia, terapia con biologici o qualsiasi terapia sperimentale secondo quanto descritto nel protocollo • Soggetto che presenta note metastasi non controllate a carico del sistema nervoso centrale (SNC). I soggetti con metastasi cerebrali sono idonei se soddisfano i requisiti previsti dal protocollo. • Soggetto che presenta uno o più condizioni clinicamente significative secondo quanto descritto nel protocollo • Soggetto che presenta eventi avversi clinicamente significativi di grado = 2 non risolti e causati da pregressa terapia antitumorale, ad eccezione di alopecia o anemia. • Soggetto sottoposto a interventi chirurgici maggiori nei 21 giorni precedenti la prima dose di telisotuzumab vedotin • Soggetto non deve avere storia di malattia polmonare interstiziale oppure di polmonite per cui sia stato necessario il trattamento con steroidi sistemici |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate (ORR) |
Tasso di risposta globale (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Overall response rate assessed by an independent central review according to RECIST, version 1.1.10 ORR will be defined as the proportion of subjects with a confirmed complete response (CR) or confirmed partial response (PR) based on RECIST, version 1.1. |
Tasso globale di risposta valutato da un servizio centrale indipendente di valutazione in base ai criteri RECIST versione 1.1.10 ORR sarà come la percentuale di soggetti con risposta completa (CR) confermata oppure con risposta parziale (PR) confermata in base ai criteri RECIST, versione 1.1. |
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E.5.2 | Secondary end point(s) |
1. Duration of Response (DoR) 2. Disease Control Rate (DCR) 3. Duration of Disease Control (DDC) 4. Progression-Free Survival (PFS) 5. Overall Survival (OS) |
1. Durata della risposta (DoR) 2. Tasso di controllo della malattia (DCR) 3. Durata del controllo della malattia (DDC) 4. Sopravvivenza libera da progressione (PFS) 5. Sopravvivenza globale (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time from the subject's initial response (CR or PR) to the first occurrence of radiographic progression determined by an independent central review or death from any cause for the responders. 2. Percentage of subjects with best overall response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks (2 tumor assessments) following enrollment, based on RECIST version 1.1. 3. Time from initial subject's response of SD, PR or CR to the first occurrence of radiographic progression determined by an ICR or death from any cause. 4. Time from subject's first dose of study drug until first occurrence of radiographic progression determined by an independent central review or death from any cause. 5. Time from subject's first dose of study drug until death from any cause. |
1. Tempo dalla risposta iniziale (CR o PR) fino al primo manifestarsi di progressione radiografica accertata da valutazione indipendente centralizzata o al decesso per qualsiasi causa per i soggetti responders. 2. Percentuale di soggetti con la migliore risposta globale di CR confermata, PR confermata o malattia stabile (stable disease, SD) per almeno 12 settimane (2 valutazioni del tumore) dopo l'arruolamento in base ai criteri RECIST, versione 1.1 3. Tempo dall’iniziale risposta SD, PR o CR fino al primo manifestarsi di progressione radiografica accertata da valutazione indipendente centralizzata o al decesso 4. Tempo dalla prima dose fino al primo manifestarsi di progressione radiografica accertata da una valutazione indipendente centralizzata 5. Tempo dalla prima dose fino al decesso |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 | Information not present in EudraCT |
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 |
Canada |
China |
Israel |
Japan |
Korea, Republic of |
Puerto Rico |
Russian Federation |
Taiwan |
Turkey |
United States |
Switzerland |
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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 end-of-study is defined as the date of the last subject's last visit or date of last follow-up contact with the subject, whichever is later. |
La fine dello studio clinico è definita come la data dell’ultima visita dell’ultimo soggetto oppure la data dell’ultimo contatto di follow-up con il soggetto, quale dei due si verifichi per ultimo |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |