An Open-Label Randomized Active-Controlled Phase II Clinical Study to Assess the Efficacy and Safety of Afuresertib Plus Paclitaxel Versus Paclitaxel in Patients with Platinum-Resistant Ovarian Cancer

An Open-Label Randomized Active-Controlled Phase II Clinical Study to Assess the Efficacy and Safety of Afuresertib Plus Paclitaxel Versus Paclitaxel in Patients with Platinum-Resistant Ovarian Cancer I, the undersigned, have reviewed and approved version 2.0 of the clinical study protocol with the date of 24 December 2019. A total of approximately 141 patients with PROC are planned to be enrolled and randomized with a 2:1 ratio in an open-label manner to the 2 arms (94 patients in the combination treatment arm and 47 patients in the paclitaxel arm) for efficacy and safety evaluation. The randomization will be stratified by site, country: US vs China, duration of the platinum free interval (PFI): 1-3 months vs >3-6 months and number of prior platinum-based therapy treatments (1/2 versus 3 prior platinum regimens). The study will consist of 4 periods. The first period is the Screening Period (Day -28 to -1) during which patients are screened for eligibility according to the inclusion and exclusion criteria. The second period is defined as Day 0, which is a mono-treatment of afuresertib in the combination treatment arm for the PK study in order to measure afuresertib PK after a single dose. The third period is a Treatment Evaluation Period with a randomized, open-label, two-arm parallel design (from starting study treatment until patients have progressive disease [PD], unacceptable toxicity, death, or withdrawal of consent). The PK study will continue in both the combination treatment arm and control arm. The fourth period is a Follow-up Period (safety evaluation at 30 days after the last dose of study treatment and OS and PFS follow-up). Patients will be tested at baseline for phosphoinositide 3 kinase (PI3K)/AKT/PTEN pathway alterations, BRCA1/2 mutations and/or level of phospho-AKT by IHC; the correlation of the efficacy endpoints and biomarker status will be analyzed retrospectively as an exploratory endpoint