Clin Cancer Res. 2026 Apr 28. doi: 10.1158/1078-0432.CCR-25-4126. Online ahead of print.
ABSTRACT
PURPOSE: Familial adenomatous polyposis (FAP) confers a significant risk of colorectal/duodenal cancer. Encapsulated rapamycin (eRapa) has demonstrated promise as FAP chemoprevention in early clinical studies.
METHODS: 30 FAP patients enrolled to three dosing regimens of eRapa (0.5 mg): cohort 1 – every other day, cohort 2 – daily every other week, or cohort 3 – daily. The primary endpoints were safety/tolerability, pharmacokinetics, and percentage change from baseline (PCFB) in colorectal polyp burden (CPB) at 6 mos. Secondary endpoints included PCFB total (TPB) and duodenal (DPB) polyp burden, and change in InSiGHT stage and Spigelman score at 6 and 12 mos.
RESULTS: 29/ 30 patients (97%) completed the 12-mos study with predictable bioavailability. Low grade adverse events were frequent, but most pronounced in daily dosing. Two patients discontinued treatment related to toxicity. Cohort 1 had the largest decrease median PCFB CPB, DPB, and TPB at 6 mos: -39.4 % (IQR, 108.9; p = 0.28), -33.33 % (IQR, 90.0; p = 0.04), and -38.6 % (IQR, 88.5; p = 0.26), respectively. At 12 mos, Cohort 2 had the largest decrease median PCFB CPB and TPB: -29.3 % (IQR, 67.6; p = 0.37) and -26.3 % (IQR, 49.5; p = 0.29), respectively. Intermittent dosing cohorts (1 & 2) reduced DPB at 6 mos (p = 0.04), and improved TPB at 12 mos (p = 0.05) compared to daily dosing.
CONCLUSION: eRapa was safe, tolerable and showed preliminary efficacy for FAP chemoprevention. The 0.5 mg daily every-other-week schedule will be evaluated in an upcoming phase III trial.
PMID:42048421 | DOI:10.1158/1078-0432.CCR-25-4126