Journal article
Phase IB dose escalation and expansion study of akt inhibitor afuresertib with carboplatin and paclitaxel in recurrent platinum-resistant ovarian cancer
SP Blagden, AL Hamilton, L Mileshkin, S Wong, A Michael, M Hall, JC Goh, AS Lisyanskaya, M DeSilvio, E Frangou, EA Stronach, P Gopalakrishna, TM Meniawy, H Gabra
Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2019
Abstract
Purpose: Preclinically, AKT kinase inhibition restores drug sensitivity in platinum-resistant tumors. Here the pan-AKT kinase inhibitor afuresertib was given in combination with paclitaxel and carboplatin (PC) in patients with recurrent platinum-resistant epithelial ovarian cancer (PROC) and primary platinum-refractory ovarian cancer (PPROC). Patients and Methods: Part I was a combination 3þ3 dose escalation study for recurrent ovarian cancer. Patients received daily continuous oral afuresertib at 50–150 mg/day with intravenous paclitaxel (175 mg/m 2 ) and carboplatin (AUC5) every 3 weeks for six cycles followed by maintenance afuresertib at 125 mg/day until progression or toxicity. Part II ..
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Funding Acknowledgements
Y The study was designed by the lead investigators and the sponsor (GlaxoSmithKline; afuresertib subsequently became an asset of Novartis Pharma AG). The sponsor collected and analyzed the data in conjunction with the authors. Early versions of this manuscript were supported by Matthew Naylor and funded by Novartis Pharmaceuticals Corporation. This work was also supported by the BRC, ECMC, and CRUK Clinical Centres, and the Ovarian Cancer Action Research Centre, Imperial College London.