Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers.
Hepatology
; 78(3): 758-770, 2023 09 01.
Article
en En
| MEDLINE
| ID: mdl-36999533
ABSTRACT
BACKGROUND AND AIMS:
Biliary tract cancers are rare, heterogeneous cancers with poor prognoses. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-ßRII (a TGF-ß "trap") fused to a human IgG1 monoclonal antibody blocking programmed death ligand 1, was evaluated in patients with locally advanced/metastatic chemorefractory biliary tract cancers. APPROACH ANDRESULTS:
This multicenter, single-arm, open-label, phase 2 study (NCT03833661) enrolled adults with locally advanced or metastatic biliary tract cancer that was intolerant to or had failed first-line systemic platinum-based chemotherapy. Patients received 1200 mg bintrafusp alfa intravenously Q2W. The primary endpoint was confirmed objective response according to Response Evaluation Criteria in Solid Tumors 1.1 assessed by IRC. Secondary endpoints included duration of response, durable response rate, safety, progression-free survival, and overall survival.Between March 2019 and January 2020, 159 patients were enrolled. Median follow-up was 16.1 (range, 0.0-19.3) months; 17 patients (10.7%; 95% CI 6.4%-16.6%) achieved an objective response. Median duration of response was 10.0 (range, 1.9-15.7) months; 10 patients (6.3%; 95% CI 3.1%-11.3%) had a durable response (≥6 mo). Median progression-free survival was 1.8 months (95% CI 1.7-1.8 mo); median overall survival was 7.6 months (95% CI 5.8-9.7 mo). Overall survival rates were 57.9% (6 mo) and 38.8% (12 mo). Grade ≥3 adverse events occurred in 26.4% of patients, including one treatment-related death (hepatic failure). Frequent grade ≥3 adverse events included anemia (3.8%), pruritus (1.9%), and increased alanine aminotransferase (1.9%).CONCLUSIONS:
Although this study did not meet its prespecified primary endpoint, bintrafusp alfa demonstrated clinical activity as second-line treatment in this hard-to-treat cancer, with durable responses and a manageable safety profile.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de los Conductos Biliares
/
Neoplasias del Sistema Biliar
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Hepatology
Año:
2023
Tipo del documento:
Article
País de afiliación:
Corea del Sur