Messaggi chiave
- TROPION-PanTumor01 è uno studio di fase 1 di incremento ed espansione della dose volto a valutare sicurezza, tollerabilità, attività antitumorale e farmacocinetica dell’anticorpo monoclonale farmaco-coniugato datopotamab deruxtecan (Dato-DXd) in pazienti con tumori solidi precedentemente trattati. In questa sede, vengono riportati i dati relativi alle pazienti con carcinoma mammario (BC) luminale o triplo negativo (TNBC) in stadio avanzato/metastatico.
- Al cut-off dei dati, il tasso di risposta obiettiva confermata e la sopravvivenza libera da progressione mediana sono stati del 26,8 e 31,8% e di 8,3 e 4,4 mesi nelle coorti BC HR+/HER2- e TNBC, rispettivamente. Eventi avversi emergenti dal trattamento (TEAE) di grado ≥3 sono stati osservati nel 41,5 e 52,3% delle pazienti delle due coorti. La stomatite è stato il TEAE più comune, con una frequenza di eventi di grado ≥3 pari rispettivamente al 9,8 e 11,4%.
- In una popolazione di pazienti con BC HR+/HER2- e TNBC pesantemente pretrattate, Dato-DXd ha dimostrato un’attività clinica promettente e un profilo di sicurezza gestibile, particolarmente a confronto con le attuali terapie standard in questo setting. La molecola è in fase di valutazione in studi di fase 3.
Abstract
Purpose
- Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker.
Patients and Methods
- TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors.
- The primary study objective was to assess the safety and tolerability of Dato-DXd.
- Secondary objectives included evaluation of antitumor activity and pharmacokinetics.
- Results from patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) or triple-negative BC (TNBC) are reported.
Results
- At data cutoff (July 22, 2022), 85 patients (HR+/HER2- BC = 41, and TNBC = 44) had received Dato-DXd. The objective response rate by blinded independent central review was 26.8% (95% CI, 14.2 to 42.9) and 31.8% (95% CI, 18.6 to 47.6) for patients with HR+/HER2- BC and TNBC, respectively.
- The median duration of response was not evaluable in the HR+/HER2- BC cohort and 16.8 months in the TNBC cohort. The median progression-free survival in patients with HR+/HER2- BC and TNBC was 8.3 and 4.4 months, respectively.
- All-cause treatment-emergent adverse events (TEAEs; any grade, grade ≥3) were observed in 100% and 41.5% of patients with HR+/HER2- BC and 100% and 52.3% of patients with TNBC. Stomatitis was the most common TEAE (any grade, grade ≥3) in both HR+/HER2- BC (82.9%, 9.8%) and TNBC (72.7%, 11.4%) cohorts.
Conclusion
- In patients with heavily pretreated advanced HR+/HER2- BC and TNBC, Dato-DXd demonstrated promising clinical activity and a manageable safety profile. Dato-DXd is currently being evaluated in phase III studies.