A phase II, open-label study to improve compliance and time of treatment after obtaining complete response (CR) through a tailored schedule of sonidegib in locally advanced basal cell carcinomas (laBCC): The SONIBEC trial.

Abstract

9540 Background: Sonidegib is an efficacious treatment of LA laBCC but is associated with a high risk of treatment-related adverse events (TRAEs) causing treatment discontinuation. Following a CR, treatment discontinuation rate reaches up to 60% after a year, leading to 3 years relapse free survival rate of 35%. We aimed at evaluating sonidegib tailored schedule (TS) after CR to increase treatment duration by reducing TRAEs, thus allowing CR maintenance. Methods: We conducted a multicenter, open-label, single-arm phase II study enrolling adult patients (pts) with laBCC who obtained a CR to sonidegib regardless of the tumor’s subtype and burden. Eligible pts received TS1 with sonidegib 14 days on and 14 days off. Pts on TS1 who experienced grade 2-3 toxicity (except alopecia) lasting >28 days moved to TS2 (7 days on and 21 days off). Treatment continued until progression or unacceptable toxicity. Primary endpoint was the rate of pts maintaining sonidegib 12 months after study enrolment (H0 31%, H1 60%). Evaluable pts were defined as all pts who were either on treatment or suspended treatment for reasons other than treatment-unrelated adverse events or death. Secondary endpoints were safety, treatment compliance, rate of disease relapse at 1 and 2 years, overall survival, quality of life, use of concomitant medications and of medical resources, and translational analysis. Results: Between Jan 2021 and Dec 2023, 22 pts from 10 Italian centers were enrolled; the data cut-off was Jan 2025. Pts characteristics are reported in table 1. The median follow-up was 22 months (range 2-33). Three disease and treatment-unrelated deaths occurred before completing 1 year of TS and therefore 19 pts were evaluable. At data cut-off, 12 pts had discontinued treatment: 26% (5) due to disease progression, 11% (2) to sonidegib’s unacceptable toxicity, the remaining either to personal or physician’s choice. Twelve out of 19 evaluable pts (63%) were still on treatment after 1 year from TS start (median duration 20 months, range 2-29), meeting the primary endpoint. The most common TRAEs episodes were muscle cramps (13), alopecia (6), dysgeusia (5) with overall TRAEs grade G1 (29), G2 (11), G3 (3). Twelve pts had dose reduction to TS2. Conclusions: Tailored maintenance schedule with pulsed sonidegib allows for longer treatment duration and fewer relapses in CR laBCC pts. Study follow up to evaluate secondary endpoints outcome and translational analysis are ongoing. Clinical trial information: 2020-002613-17 . Patient characteristics. Characteristic N (%) Male : Female 14 (64) : 8 (36) Median age 76y (range 56-93y) ECOG PS 0-1 15 (68): 7 (32) Histology sub-type Nodular 8 (36) Superficial 2 (9) Infiltrative 7 (32) Mixed 1 (5) Other 4 (18)