Introduction Relapse of OC within 6 months after the last dose of platinum-based therapy is defined as platinum-resistant OC (PROC). Non-platinum therapies for PROC results in a progression-free survival (PFS) of 3.5–4 months and overall-response rate (ORR) of 10–20%. Therefore, developing new therapies for PROC remains an unmet medical need. Afuresertib (GSK2110183), a new oral, small-molecule pan-AKT kinase inhibitor, can reduce AKT activity in cancers and re-sensitize tumor cells to taxanes when used as a combination therapy. In addition, afuresertib plus chemotherapy has demonstrated anti-tumor efficacy (ORR 32% with mPFS of 7.1 months) with acceptable safety profiles. Therefore, the combination of afuresertib plus weekly paclitaxel warrants investigation in PROC.

Methods This is an open-label randomized active-controlled global phase II clinical study assessing the efficacy and safety of afuresertib (125 mg PO qD) plus paclitaxel (80 mg/M2 IV D1,8,15) q3W versus paclitaxel in PROC patients. Primary endpoint is PFS ( RECIST 1.1). Secondary endpoints include: OS, ORR, DOR, DCR, CA-125 response, etc. A total of 141 patients with PROC from both USA and China will be randomized 2:1 to combination and paclitaxel only arms, respectively. Inclusion criteria is histologic/cytologic confirmed high-grade serous, endometroid, or clear cell OC with 1 to 3 prior systemic therapies. Patients must either have received or be ineligible for prior bevacizumab and/or PARP inhibitor.

Results First patient was enrolled and dosed 7/7/2020 with planned study completion in mid-2022.

Conclusion/Implications New PROC afuresertib trial is now available for enrollment in US and China (NCT04374630).