1932P - First in human trial of CEB-01 for retroperitoneal soft tissue sarcoma

Background

Local recurrence after radical surgery for retroperitoneal soft tissue sarcoma (RPS) occurs in 41–50% of patients and constitutes a major cause of death. CEB-01 is a biocompatible and biodegradable membrane implant with PLGA nanofibers entangled with SN-38 for a steady delivery. When placed in the surgical bed after RPS resection, it may increase local control rates and survival.

Methods

This is a multicentre, first in human trial (EudraCT: 2018-001026-25) following a 3+3 dose escalation design, and an expansion cohort at the recommended phase II dose (RP2D). Efficacy is evaluated using RECIST 1.1. Primary objective is RP2D. Safety, pharmacokinetics (PK) are secondary objectives.

Results

At present, 10 patients (pts) have been enrolled: 3 female / 7 male; mean age 62.1 years (40 - 77) with dedifferentiated liposarcoma (LPS) (5 cases), well differentiated LPS (3), LPS (1), and leiomyosarcoma (1). 7 pts had unresected primary lesions, and 3 were locoregional relapses. Post-surgery margins were R0 (7), R1 (2) and unknown (1). CEB-01 was implanted in 3 dose-increasing cohorts: 1st) 2 membranes of 180 cm² each, 25 mcg/cm², total 9 mg; 2nd) 2 x 180 cm², 50 mcg/cm², total 18 mg and 3rd) 4 x 180 cm², 50 mcg/cm², total 36 mg. No dose limiting toxicity (DLT) has been observed in any of the cohorts. The expansion phase is ongoing. Adverse events are similar to those post-surgery of RPS. Death (3 pts), after abdominal infection, bleeding (both unrelated) or retroperitoneal haemorrhage (related). After a median follow-up of 16.3 months (2.1 to 24.9), 2 (with the lower dose) local recurrences in the area of the implant have been observed after 5.5- and 8.6-months post-surgery. 2 pts completed 24 months of follow-up. In 5 ongoing pts no recurrences have been observed after 2.1 to 17.8 months of follow-up (median 16.2 months). SN-38’s PK shows dose linearity, half-life ranging from 287 - 372 hours, Cmax: 0.76 - 3.58 ng/ml and AUC 0-t: 118 - 321 ng/ml*h. Blood levels of SN-38 were detectable 28 days after surgery.

Conclusions

With CEB-01 no DLT has been observed. Local recurrence occurred in 2 out of 10 pts at 5.5- and 8.6-months post-surgery. CEB-01 provides a local steady and prolonged release of SN-38, with a much lower Cmax than when SN-38 is administered as irinotecan.

Clinical trial identification

NCT04619056.

Editorial acknowledgement

Legal entity responsible for the study

Cebiotex S.L.

Funding

Cebiotex S.L.

Disclosure

A. Perez Campos: Financial Interests, Personal, Advisory Board: Cebiotex. F. Cano Casas: Financial Interests, Personal, Stocks or ownership, shareholder of Cebiotex, S.L. through the society Cebfunding, S.L.: Cebiotex SL. J.A. Tornero García: Financial Interests, Personal, Stocks or ownership, shareholder: Cebiotex S.L.; Financial Interests, Personal, Leadership Role, CTO of Cebiotex, S. L.: Cebiotex S.L.. L. Marti: Financial Interests, Personal, Stocks or ownership, shareholder: Cebiotex. L. Krauel: Financial Interests, Personal, Leadership Role, CSO and cofounder: Cebiotex. All other authors have declared no conflicts of interest.