Portal de investigación
First-in-Human Study of CEB-01: Novel Loco-Regional SN-38-Releasing Membrane to Prevent Local Recurrence in Retroperitoneal Sarcomas
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Gonzalez J.A.
- Sebio A.
- Martin-Broto J.
- Hindi N.
- Villarejo-Campos P.
- Jiménez M.
- Álvarez Álvarez R.
- Asencio J.M.
- Serrano C.
- Rodríguez Conde N.
- Castro Boix S.
- Krauel L.
- Colom Codina H.
- Tornero García J.A.
- Lopera de Llanos E.
- Huguet Ninou A.
- Pérez Campos A.
- Gruber A.-K.
- López Pousa A.
Grupos
Abstract
Background: Retroperitoneal sarcoma (RPS) resection remains challenging, with up to 50% of patients developing local recurrence and a 5-year survival rate of 50%. CEB-01, designed for local and controlled SN-38 delivery postresection, may increase local control and survival rates. Materials and Methods: CEB-01 is a first-in-human, multicenter trial following a 3+3 dose escalation design and expansion cohort conducted in six centers in Spain. CEB-01 was implanted at three dose levels of SN-38: 9, 18, and 36 mg. The objectives were to establish the recommended phase 2 dose (RP2D) and evaluate its safety, efficacy, and pharmacokinetics. Results: From July 2020 to November 2023, 14 patients were included: 10 males, with a median age of 63 years (range: 40–76), mostly with dedifferentiated (50%) and well-differentiated liposarcoma (35.7%), and R0 (79%) and R1 (21%) postsurgical margins. No dose-limiting toxicities were observed, and the RP2D was set at 18 mg. With a median follow-up of 9.1 months (range: 1–21), all patients at RP2D were recurrence-free and alive. Grade = 3 adverse events were reported in just one patient treated with RP2D. The pharmacokinetic profile of SN-38 showed substantially lower Cmax (20–70-fold) and longer elimination half-life times than those of intravenous irinotecan at clinically relevant doses. CEB-01 showed prolonged release of SN-38, which was detectable after 28 days in circulating blood. Conclusions: CEB-01 at 18 mg exhibited a tolerable safety profile and preliminary efficacy against postsurgery recurrence in patients with RPS. These results warrant further clinical investigations of this type of tumor. Clinical trial identification: EU CT: 2024-516971-34-00; clinicaltrials.gov: NCT04619056. © Society of Surgical Oncology 2026.
Datos de la publicación
- ISSN/ISSNe:
- 1068-9265, 1534-4681
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 41998462
- Enlace a otro recurso:
- www.scopus.com
- Factor de Impacto:
- 1,158 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
ANNALS OF SURGICAL ONCOLOGY SPRINGER
Citas Recibidas en Web of Science: 1
Documentos
- No hay documentos
Filiaciones
Keywords
- CEB-01; Drug-release membrane; First-in-human; Retroperitoneal sarcoma; RP2D; SN-38
Campos de Estudio
Cita
Gonzalez JA,Sebio A,Martin J,Hindi N,Villarejo P,Jiménez M,DÍAZ R,ORBIS JF,LÓPEZ R,Álvarez R,Asencio JM,Serrano C,Rodríguez N,Castro S,Krauel L,Colom H,Tornero JA,Lopera de Llanos E,Huguet A,Pérez A,Gruber A-K,López A. First-in-Human Study of CEB-01: Novel Loco-Regional SN-38-Releasing Membrane to Prevent Local Recurrence in Retroperitoneal Sarcomas. Ann. Surg. Oncol. 2026. 33. (8):p. 7677-7687. IF:3,800. (1).