A phase II study of Navitoclax (ABT-263) as single agent in women heavily pretreated for recurrent epithelial ovarian cancer: The MONAVI - GINECO study.

ABSTRACT

BACKGROUND: There are limited treatment options for ovarian cancer patients with early relapse after platinum chemotherapy. In preclinical studies, we previously demonstrated the promising activity of ABT-737, a Bcl-2/Bcl-xL anti-apoptotic protein inhibitor, in chemo-resistant ovarian cancer cells and tumors, suggesting its potential activity in platinum-resistant patients. METHODS: We conducted a prospective multicenter single-arm phase II study to assess the efficacy of Navitoclax (orally available ABT-737 analogue) monotherapy in 46 heavily pretreated (2-12 lines, median = 4) patients with high-grade serous platinum-resistant ovarian tumors. Navitoclax was administered at the daily dose of 150 mg during a lead-in period (7-14 days) and then increased to 250 mg daily in the absence of dose-limiting thrombocytopenia (Progression-free survival (PFS) based on RECIST v1.1 criteria was the primary endpoint. Analysis of efficacy according to the expression of Bcl-2 family proteins in tumor biopsies was also planned.

RESULTS:

The 3-month PFS was 22.7% [95%CI 13.2-39.2], median PFS was 1.64 months [95%CI 1.58-2.30]. There were 16 (35.6%, 95%CI 22.3-51.3) overall responses (RECIST v1.1) 1 partial response and 15 stable diseases. No correlation between the expression of Bim, Mcl-1 and P-ERK with clinical response was found in this study. Thrombocytopenia was the major side-effect (G3/4 n = 12; 26%), leading to pursue at the daily dose of 150 mg in 8 patients and to discontinue treatment in 3 patients. Neither significant bleeding nor toxic death were observed.

CONCLUSIONS:

Navitoclax monotherapy had poor activity that was not correlated with the expression of Bim, Mcl-1 and P-ERK, without unacceptable toxicity. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT02591095.