LINFOMA NEWS – Sospensione dell’arruolamento nello studio LOTIS-9 dopo la morte di 7 pazienti e 5 eventi avversi gravi. Lo studio sta valutando Zynlonta nel trattamento del linfoma diffuso a grandi cellule B
ADC Therapeutics ha sospeso l’arruolamento nello studio LOTIS-9 riguardante il coniugato anticorpo-farmaco Zynlonta associato a Rituximab dopo la morte di 7 pazienti e altri 5 eventi avversi gravi su 40 pazienti arruolati
ADC Therapeutics ha sospeso l’arruolamento in uno studio di combinazione di fase 2 LOTIS-9 sul coniugato anticorpo-farmaco Zynlonta ( Loncastuximab tesirine ), mentre sta indagando su 7 decessi di pazienti e altri 5 gravi eventi respiratori tra i pazienti che hanno ricevuto il farmaco.
I ricercatori avevano arruolato 40 pazienti unfit o fragili con linfoma diffuso a grandi cellule B ( DLBCL ) precedentemente non-trattato.
Dopo aver ricevuto Loncastuximab tesirine, 12 di loro hanno manifestato eventi avversi correlati alle vie respiratorie.
I ricercatori hanno, tuttavia, concluso che 11 degli eventi, tra cui 6 decessi, non sarebbero correlati al trattamento con Zynlonta o probabilmente non erano correlati al farmaco.
Tutti i pazienti deceduti soffrivano di almeno una comorbilità significativa, tra cui malattia polmonare ostruttiva, edema polmonare, bronchiectasie croniche, fibrosi polmonare idiopatica o recente infezione da COVID-19. Tutti i pazienti deceduti avevano almeno 80 anni.
ADC Therapeutics ha dichiarato di aver messo lo studio in “pausa volontaria” per avere più tempo per la valutazione dei dati … e determinare i passi successivi. Lo studio stava testando Loncastuximab tesirine in combinazione con Rituximab.
ADC Therapeutics ha informato sia la FDA ( l’Agenzia regolatoria degli Stati Uniti ) che l’EMA ( l’Agenzia regolatoria europea ).
La Società che produce Zynlonta non prevede di riportare ulteriori dati di sperimentazione entro la fine dell’anno.
Zynlonta aveva ottenuto l’approvazione nel 2021 nell’ambito del percorso accelerato della FDA come trattamento in monoterapia per pazienti adulti con linfoma DLBCL recidivante o refrattario dopo due precedenti linee di terapia.
Loncastuximab tesirine è il primo coniugato anticorpo-farmaco mirato diretto a CD19 a singolo agente ad avere “cleared” la malattia dopo aver registrato un tasso di risposta globale del 48,3% in uno studio di fase 2.
LINK: https://www.fiercepharma.com/pharma/adc-therapeutics-puts-zynlonta-study-enrollment-pause-after-seven-patient-deaths-five-other–
COMUNICATO STAMPA ADC THERAPEUTICS
ADC Therapeutics: voluntary pause of enrollment in the phase 2 LOTIS-9 clinical trial of Loncastuximab tesirine and Rituximab in unfit or frail previously untreated DLBCL patients
ADC Therapeutics has announced a voluntary pause in the enrollment of new patients in the phase 2 LOTIS-9 clinical trial evaluating Loncastuximab tesirine ( Zybnlonta ) and Rituximab in unfit or frail patients with previously untreated diffuse large B-cell lymphoma ( DLBCL ).
The voluntary action was taken by ADC Therapeutics after a recent review of aggregate data of the 40 patients enrolled in the trial and consultation with the Data Monitoring Committee ( DMC ) which signaled potentially excessive respiratory-related events.
These respiratory-related treatment-emergent adverse events ( TEAEs ) included seven grade 5 fatal events and five grade 3 or grade 4 respiratory-related TEAEs.
As per investigator assessment, 11 of the 12 events ( including 6 of the 7 grade 5 fatal events ) were individually assessed as unlikely or unrelated to study drug. Four out of the 5 grade 3 or grade 4 events have since resolved and the patients have completed treatment per protocol.
The cause of these events remains under further investigation.
All patients with fatal events had one or more significant active underlying respiratory and/or cardiac co-morbidities including severe chronic obstructive pulmonary disease ( COPD ), pulmonary edema, chronic bronchiectasis, idiopathic pulmonary fibrosis and recent COVID-19 infection and all were greater than or equal to 80 years of age.
The mean age was 82.7 years and the mean number of days from the last dose to death was 51 days, with a range of 19 to 86 days.
It is important to note that all twelve of the patients with grade 3-5 TEAEs in the LOTIS-9 study would have been excluded from the LOTIS-5 trial.
ADC Therapeutics’ decision to pause enrollment enables time to evaluate data around the TEAEs and determine next steps.
ADC Therapeutics has notified all study investigators and regulatory authorities including the U.S. Food and Drug Administration ( FDA ) and the European Medicines Agency ( EMA ) of the decision to pause enrollment.
The U.S. FDA and the EMA have approved Zynlonta for the treatment of adult patients with relapsed or refractory ( r/r ) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma.
The trial has included a broad spectrum of heavily pre-treated patients ( median three prior lines of therapy ) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double / triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with Zynlonta. This indication was approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
LINK: https://ir.adctherapeutics.com/press-releases/press-release-details/2023/ADC-Therapeutics-Announces-Voluntary-Pause-of-Enrollment-in-the-Phase-2-LOTIS-9-Clinical-Trial-of-ZYNLONTA-loncastuximab-tesirine-lpyl-and-Rituximab-in-Unfit-or-Frail-Previously-Untreated-DLBCL-Patients/default.aspx
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