First-in-human phase I study of CEB-01, a biodegradable SN-38–releasing membrane, to prevent local recurrence after resection of retroperitoneal sarcoma: Updated results.

Abstract

e23559 Background: Local recurrence is the main cause of mortality in retroperitoneal sarcoma (RPS), and perioperative systemic therapies have shown limited benefit. CEB-01 is a biodegradable PLGA membrane designed for loco-regional delivery of SN-38 to the surgical bed. We report updated safety, pharmacokinetic, and efficacy data from this first-in-human phase I study. Methods: This multicenter, open-label phase I trial followed a 3+3 dose-escalation design with expansion at the recommended phase 2 dose (RP2D). CEB-01 was implanted after tumor resection at SN-38 doses of 9, 18, or 36 mg. Primary objectives were RP2D determination and safety. Secondary objectives included pharmacokinetics and preliminary efficacy. Local recurrence was defined as relapse within the membrane-covered area. Results: Between July 2020 and November 2023, 14 patients were enrolled (median age 63 years; 71% male). Most tumors were liposarcomas (93%), de novo (64%) and R0 resection in 79%. No dose-limiting toxicities were observed. Following safety review, 18 mg was established as RP2D. In that cohort, after a median follow-up of 13.8 months, a local recurrence was observed within the treated area in 1 patient receiving RP2D. No deaths have been reported. Grade ≥3 treatment-related adverse events occurred in one patient (12.5%) at RP2D. PK analysis showed sustained SN-38 release with up to 70-fold lower Cmax, a half-life (~300 hours) compared with SN-38 PK values after intravenous irinotecan, with detectable plasma levels up to 28 days. Conclusions: Updated data confirm that CEB-01 at 18 mg has an acceptable safety profile and promising local control in RPS. Prolonged loco-regional delivery of SN-38 may represent a novel strategy to reduce post-surgical local recurrence. Further clinical investigation Phase 2/3 is warranted. Clinical trial information: NCT04619056 .