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We conducted a single-arm single-center phase 2 study of TAS-117 in heavily treated patients with tumors refractory to systemic chemotherapy and harboring phosphatidylinositol 3-kinase (PI3K)\/Akt mutations. Patients with gastrointestinal (GI) cancers were orally administered 16\u00a0mg TAS-117 daily, and those with non-GI tumors were administered 24\u00a0mg on a 4 days on\/3 days off schedule. The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, safety, and tolerability. Thirteen patients were enrolled: eight with non-GI (breast, ovarian, endometrial, and non-small cell lung) and five with GI (colon, rectal, gastric, and gallbladder) cancers. Ten patients were treated with TAS-117 after <jats:underline>\u2265<\/jats:underline>\u20094 lines of therapy. Twelve patients showed PIK3 catalytic subunit alpha (<jats:italic>PIK3CA<\/jats:italic>) mutations; one harbored an Akt1<jats:sup>E17K<\/jats:sup> mutation. The median treatment duration was 1.4 months; the median number of treatment cycles was 2. The ORR was 8\u2009%, and DCR was 23\u2009%. The median PFS and OS were 1.4 and 4.8 months, respectively. Grade 3\u20134 treatment-related adverse events were anorexia (grade 3, 8\u2009%) and hyperglycemia (grade 3, 8\u2009%; grade 4, 8\u2009%).Grade 3\u20134 treatment-related adverse events occurred in 27\u2009% of grade 3 anorexia (9\u2009%) and hyperglycemia (grade 3, 8\u2009%; grade 4, 9\\%). TAS-117 showed limited antitumor activity and manageable toxicity. Clinical efficacy was observed in patients with ovarian cancer harboring <jats:italic>PIK3CA<\/jats:italic> E545K mutations and in patients with breast cancer harboring <jats:italic>PIK3CA<\/jats:italic> H1047R and Akt1<jats:sup>E17K<\/jats:sup> mutations.<\/jats:p><jats:p>Trial registration: This study was retrospectively registered with ClinicalTrial.gov (NCT03017521 on January 11, 2017).<\/jats:p>","DOI":"10.1007\/s10637-021-01085-7","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T19:03:04Z","timestamp":1615834984000},"page":"1366-1374","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Phase 2 study of TAS-117, an allosteric akt inhibitor in advanced solid tumors harboring phosphatidylinositol 3-kinase\/v-akt murine thymoma viral oncogene homolog gene mutations"],"prefix":"10.1007","volume":"39","author":[{"given":"Jii Bum","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyu","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hoon","family":"Beom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun Min","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Ryun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hyuk","family":"Sohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong Bae","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Young","family":"Rha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Cheol","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"1085_CR1","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nrd2926","volume":"8","author":"P Liu","year":"2009","unstructured":"Liu P, Cheng H, Roberts TM, Zhao JJ (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. 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