Abstract CT151: Phase 2 study of TAS-117 in advanced solid tumors harboringphosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene aberrations
Authors: Lee Jii Bum , Jung Minkyu , Beom Seung Hoon , Kim Gun Min , Kim Hye Ryun , Sohn Joo Hyuk , Ahn Joong Bae , Rha Sun Young , Chung Hyun Cheol 
Published: July 2021

Abstract
Purpose: TAS-117 is a highly potent and selective allosteric pan-v-akt murine thymoma viral oncogene homolog (Akt) inhibitor administered orally. We conducted a single-arm, single-center, phase 2 study of TAS-117 in heavily treated patients with multiple tumors refractory to systemic chemotherapy harboring phosphatidylinositol 3-kinase (PI3K)/Akt mutations using a basket trial design. Methods: Patients with gastrointestinal (GI) cancers were administered 16 mg TAS-117 daily and those with non-GI tumors were treated with 24 mg TAS-117 for 4 days followed by a 3-day rest. The study was conducted over 21-day treatment cycles. Tumors were assessed by imaging every six weeks until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, and safety and tolerability of TAS-117. This study was registered with ClinicalTrial.gov (NCT03017521). Results: A total of 13 patients were enrolled, including eight patients with non-GI cancer (breast cancer (n = 4, 31%), ovarian cancer (n = 2, 15%), endometrial cancer (n = 1, 8%), and non-small cell lung cancer (NSCLC; n = 1, 8%)) and five patients with GI cancer (colon cancer (n = 2, 15%), rectal cancer (n = 1, 8%), gastric cancer (n = 1, 8%), and gallbladder cancer (n = 1, 8%)). The median age was 53 years (range, 34-71). The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in eight patients (62%), and 10 patients (77%) were treated with TAS-117 after &gt;4 lines of therapy. Twelve patients showed mutations in PIK3 catalytic subunit alpha (PIK3CA): E542K (n = 2, 15%), E545A (n = 1, 8%), E545K (n = 4, 31%), H1047R (n = 4, 31%), and Q546K (n = 1, 8%) One patient harbored an Akt1E17K mutation. The median treatment duration was 1.4 months (range, 0.4-3.2), and the median number of treatment cycles was 2 (range 1-5). The ORR was 8% (n = 1), and the DCR was 23% (n = 3). The median PFS was 1.4 months (95% confidence interval (CI): 1.2-1.6), and the median OS was 4.8 months (95% CI: 2.6-11.2 months). At the time of data-cut off in February 19, 2020, 9 patients had disease progression, 2 patients experienced adverse events, 1 patient withdrew from study, and 1 patient discontinued treatment due to physician's decision. Treatment-related adverse events (AEs) occurred in 85% of patients, and 27% (n = 3) experienced grade 3-4 AEs (grade 3 anorexia, n = 1, 9%) and hyperglycemia (grade 3, n = 1, 9%; grade 4, n = 1, 9%). Conclusion: TAS-117 showed limited anti-tumor activity and a manageable toxicity profile in patients with advanced solid tumors. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations, and in those with breast cancer harboring PIK3CA H1047R and Akt1E17K mutations.
Citation Format: Jii Bum Lee, Minkyu Jung, Seung Hoon Beom, Gun Min Kim, Hye Ryun Kim, Joo Hyuk Sohn, Joong Bae Ahn, Sun Young Rha, Hyun Cheol Chung. Phase 2 study of TAS-117 in advanced solid tumors harboringphosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene aberrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT151.