A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer.

OBJECTIVE: Indoleamine 2,3-dioxygenase-1 (IDO1) is a key regulator of immune tolerance in ovarian cancer. This study investigated efficacy and safety of the IDO1 enzyme inhibitor epacadostat versus tamoxifen in patients with biochemical-only recurrence (CA-125 elevation) following complete remission after first-line chemotherapy for advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. METHODS: In this open-label, phase 2 study (NCT01685255), patients were randomised 1:1 to epacadostat 600mg or tamoxifen 20mg twice daily for successive 28-day cycles and stratified by time since completion of first-line chemotherapy to first CA-125 elevation (3 to <12 or ≥12months). The primary endpoint was investigator-assessed progression-free survival (PFS; RECIST v1.1). Secondary endpoints included CA-125 response (Gynecologic Cancer InterGroup criteria), overall survival, safety, and tolerability. RESULTS: The study was terminated primarily due to slow accrual and lack of evidence of superiority. Median PFS was 3.75months for epacadostat (n=22) versus 5.56months for tamoxifen (n=20; HR, 1.34 [95% CI, 0.58-3.14]; P=0.54). Of evaluable patients, 1 (5.0%) epacadostat and 3 (15.8%) tamoxifen patients had confirmed CA-125 responses. The most common treatment-emergent adverse event was fatigue (epacadostat, 36.4%; tamoxifen, 40.0%). Immune-related adverse events, observed with epacadostat only, were primarily rash (18.2%) and pruritus (9.1%). Epacadostat pharmacokinetics/pharmacodynamics were consistent with its known mechanism of action. IDO1 expression was observed in 94% of archival tumour samples. CONCLUSIONS: This first report of immunotherapy evaluation in biochemical-only relapse ovarian cancer and of IDO1 inhibitor monotherapy in ovarian cancer found no significant difference in efficacy between epacadostat and tamoxifen. Epacadostat was generally well tolerated.