Abstract / Description
ABSTRACT Introduction Opaganib is a first‐in‐class oral sphingolipid metabolism inhibitor that inhibits sphingosinekinase 2 (SphK2) and dihydroceramide desaturase (DES) and that has a demonstrated safety and preliminary anti‐cancer activity signal in a Phase I study. Methods In this phase II trial, patients with metastatic castration‐resistant prostate cancer who had disease progression on novel hormonal agents (NHAs) abiraterone or enzalutamide were enrolled and treated with opaganib while continuing their NHA. After safety lead‐in cohorts, the trial enrolled cohort 2 (abiraterone + opaganib 500 mg Q 12 h) and cohort 3 (enzalutamide + opaganib 500 mg Q 12 h). The primary efficacy endpoint was the proportion of patients with disease control at Day 113. The postulated disease control rate was 10%. Secondary efficacy endpoints include prostate‐specific antigen (PSA) progression‐free survival (PSA‐PFS) and PSA response rates. The primary safety endpoint was the incidence of adverse events (AEs). Results The disease control rates were 15% (95% CI = 4%–35%, 4 of 26 patients) in cohort 2 and 9% (95% CI = 2%–24%, 3 of 34 patients) in cohort 3. The median PSA‐PFS was 56 days (95% CI = 35–112 days) in cohort 2 and 55 days (95% CI = 35–56 days) in cohort 3. The most common AEs of grade 3 or higher were hypertension (8%) and musculoskeletal AEs (8%) in cohort 2 and grade 3 anemia (18%) in cohort 3. Conclusion The trial did not meet its primary objective of demonstrating 30% disease control at 113 days. However, subjects who experienced a PSA response or stabilization warrant further exploration for biomarkers of response. Trial Registration ClinicalTrials.gov number: NCT04207255