DESTINY LUNG 04 - Studio di fase 3, in aperto, randomizzato, multicentrico volto a valutare l’efficacia e la sicurezza di Trastuzumab Deruxtecan come trattamento di prima linea in pazienti con NSCLC non resecabile, localmente avanzato o metastatico con mutazioni dell’esone 19 o 20 di HER2 - D967SC00001

Studio Clinico

Patologia: Neoplasie del polmone

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Partecipanti di almeno 18 anni
- Malattia localmente avanzata non condidabile a terapia curativa, o malattia metastatica
- NSCLC istologicamente documentato, non squamoso con mutazione HER2 in esoni 19 o 20 da tessuto NGS o ctDNA
- Naive al trattamento per la terapia sistemica con intento palliativo nel setting di malattia localmente avanzata o metastatica
- Frazione di eiezione ventricolare sinistra (LVEF) maggiore di 50
- Malattia misurabile valutata dal ricercatore sulla base dei criteri RECIST 1.1
- Adeguata funzionalità d'organo come indicato nel protocollo, comprese la funzione cardiaca, renale, epatica
- ECOG 0-1
- Disponibilità di tessuto tumorale per il test centralizzato.

Criteri di esclusione: 

- Tumori con alterazioni target di EGFR (o altre mutazioni selezionabili come target comprese ma non limitato ad ALK, se testato di routine in quanto alterazione targetable con la terapia disponibile approvata)
- Eventuali metastasi cerebrali clinicamente attive; metastasi cerebrali precedentemente trattate sono consentite
- Disturbi autoimmuni o infiammatori attivi
- Anamnesi di infarto miocardico entro 6 mesi prima della randomizzazione
- Anamnesi di polmonite non infettiva/ILD, ILD attuale o sospetta
- Polmone-specifico intercurrent clinico grave malattia significativa
- Controindicazione alla chemioterapia doublet a base di platino o pembrolizumab.

Trattamento sperimentale: 

Trastuzumab Deruxtecan endovena

Trattamento di controllo: 

Farmaco: Chemioterapia a base di platino a scelta dell'investigatore, Cisplatino somministrato endovena
Farmaco: Chemioterapia a base di platino a scelta dell'investigatore, Carboplatino somministrato endovena
Farmaco: Pembrolizumab endovena
Farmaco: Pemetrexed endovena

Obiettivi primari dello studio: 

Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) [ Time Frame: Until progression or death, assessed up to approximately 12 months ]
Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause

Obiettivi secondari dello studio: 

- Overall Survival (OS) [ Time Frame: Until death, assessed up to approximately 28 months. ]
Defined as time from randomization until the date of death due to any cause.
- Progression Free Survival (PFS) by investigator assessment [ Time Frame: Until progression, assessed up to approximately 12 months ]
Defined as time from randomization until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause.
- Objective Response Rate (ORR) [ Time Frame: Until progression, assessed up to approximately 12 months ]
Defined as the proportion of participants who have a complete response (CR) or partial response (PR) as assessed by Blinded Independent Central Review (BICR) and investigator according to RECIST 1.1
- Duration of Response (DoR) [ Time Frame: Until progression, assessed up to approximately 12 months ]
Defined as the time from the date of first documented response until date of documented progression as assessed by Blinded Independent Central Review (BICR) and investigator assessment according to RECIST 1.1.
- Time to second progression or death (PFS2) [ Time Frame: Assessed up to approximately 20 months ]
Defined as the time from randomization until second progression on next-line of treatment as assessed by investigator at the local site using assessments conducted per local standard clinical practice, or death due to any cause.
- Landmark analysis of PFS (PFS12) [ Time Frame: Assessed up to approximately 12 months ]
Defined as proportion of participants alive and progression-free at 12 months, as assessed by Blinded Independent Central Review (BICR) and investigator.
- Landmark analysis of OS (OS24) [ Time Frame: Assessed up to approximately 24 months ]
Defined as proportion of participants alive at 24 months
- Central Nervous System (CNS) - Progression Free Survival (PFS) [ Time Frame: Until CNS progression or death, assessed up to approximately 12 months ]
Defined as time from randomization until Central Nervous System (CNS) progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR) or death due to any cause in the absence of CNS progression.
- Safety and tolerability of T-DXd versus Standard of Care treatment [ Time Frame: Until progression or death, assessed up to approximately 28 months ]
Assessed by the occurrence of AEs, SAEs, and changes from baseline in laboratory parameters, vital signs, ECG, and ECHO/MUGA scan results.
- Pharmacokinetics (PK) of T-DXd, total anti-HER2 antibody and DXd in serum [ Time Frame: Up to cycle 4, approximately 12 weeks ]
Serum concentration of T-DXd, total anti-HER2 antibody and DXd.
- Immunogenicity of T-DXd [ Time Frame: Until progression, assessed up to approximately 13 months ]
Presence of anti-drug antibodies (ADAs) for T-DXd.
- Patient-reported pulmonary symptoms associated with Non-Small Cell Lung Cancer [ Time Frame: Until progression, assessed up to approximately 13 months ]
Time to sustained deterioration in pulmonary symptoms (cough, dyspnea, chest pain) while on treatment using the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ).
- Patient-reported tolerability of T-DXd described using symptomatic AEs [ Time Frame: Until progression, assessed up to approximately 13 months ]
Symptomatic AEs: Descriptive summary of the proportion of participants reporting symptomatic AEs while on treatment, as assessed by the Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and items from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library.
- Patient-reported tolerability of T-DXd described using overall side-effect bother [ Time Frame: Until progression, assessed up to approximately 13 months ]
Overall side-effect bother: Descriptive summary of the proportion of participants reporting overall side-effect bother on the Patient's Global Impression of Treatment Tolerability (PGI-TT) while on treatment.
- Patient-reported tolerability of T-DXd described using physical function [ Time Frame: Until progression, assessed up to approximately 13 months ]
Physical Function: The proportion of participants with maintained or improved physical function while on treatment, based on the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC-QLQ-C30) physical functioning scale.

Data di inizio dell'arruolamento: 28.10.2021

Centri partecipanti

Nord Italia

Centro Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2021-000634-33

Data di inserimento: 24.02.2022

Data di aggiornamento: 21.07.2022

Promotore

AstraZeneca

Principal Investigator ITALIA

Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano (TO)

Riferimento: Dr. Non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: Orbassano (TO)