pifusertib (TAS-117) / Otsuka - LARVOL DELTA

A first-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumors. (PubMed, Cancer Chemother Pharmacol) - "Oral doses of TAS-117 once daily up to 16 mg/day and intermittent dosing of 24 mg/day were well tolerated. TAS-117 pharmacokinetics were dose proportional at the doses evaluated. Antitumor activity may occur through AKT inhibition."

Journal • Metastases • P1 data • Oncology • Solid Tumor • AKT1S1

TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations (clinicaltrials.gov) - P1 | N=17 | Terminated | Sponsor: Taiho Oncology, Inc. | Phase classification: P2 ➔ P1 | N=96 ➔ 17 | Trial completion date: Dec 2024 ➔ Mar 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2024 ➔ Feb 2023; The Sponsor had decided to terminate this clinical trial due to an insufficient rate of accrual of patients.

Enrollment change • Metastases • Phase classification • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor • AKT1S1 • PTEN

TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations (clinicaltrials.gov) - P2 | N=96 | Active, not recruiting | Sponsor: Taiho Oncology, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • AKT1S1 • PTEN

Dose escalation of TAS-117 in patients with advanced solid tumors (ESMO 2022) - P2 | "Conclusions TAS-117 showed tolerable toxicity; durable clinical benefit associated with tumor shrinkage was observed in 1 pt. This phase II study is ongoing."

Clinical • Breast Cancer • Oncology • Solid Tumor • PTEN

[VIRTUAL] A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN inactivating mutations (ESMO 2021) - P2 | "Taiho Oncology, Inc. reviewed the abstract for scientific accuracy but had no significant input into the content."

Clinical • P2 data • Brain Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • PTEN

A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations. (PubMed, Future Oncol) - "The mechanism of action, safety and dosing regimen for the novel allosteric AKT inhibitor TAS-117 have been explored in a phase I study in Japan in which activity was observed against certain tumor types. Here we describe the study protocol of an international, two-part Phase II study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations."

Journal • P2 data • Review • Oncology • Solid Tumor • PTEN

[VIRTUAL] Phase 2 study of TAS-117 in advanced solid tumors harboringphosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene aberrations (AACR 2021) - P2 | "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."

P2 data • Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Rectal Cancer • Solid Tumor • Thymoma • Thymus Cancer • PIK3CA

The K-BASKET trial: A prospective phase II biomarker-driven multiple basket trial in Korean solid cancer patients (ESMO 2019) - "Three treatment arms for the second step are the followings; 1) Patients with MET amplification or exon 14 skipping MET mutation will be assigned to the TAS-115 arm, a novel multikinase inhibitor. 2) Patients with activating PIK3CA or AKT mutations will be assigned to the TAS-117 arm, a novel selective AKT inhibitor...Legal entity responsible for the study: Yonsei University. Funding: National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA16C0018)."

Biomarker • Clinical • IO Biomarker • P2 data • PD(L)-1 Biomarker

Taiho Oncology To Share Data in Advanced Solid Tumors at ESMO Congress 2021 (PRNewswire) - “Taiho Oncology…announced data presentations from several studies for two of its investigational agents at the European Society for Medical Oncology (ESMO) Congress 2021. Three abstracts have been selected for poster presentations, including for futibatinib (TAS-120) in advanced solid tumors, including intrahepatic cholangiocarcinoma (iCCA) and gastric cancer, and for TAS-117 in advanced solid tumors.”

Clinical data • P1 data • P2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Novel epigenetic therapies for multiple myeloma (PubMed, Rinsho Ketsueki) - "Moreover, UNC1999 and a selective Akt inhibitor TAS-117 synergistically inhibit the growth of MM cells through epigenetic mechanisms...Interestingly, a microtubule polymerization inhibitor PTC596 cooperatively downregulates BMI1 protein with proteasome inhibitors, exhibiting in-vitro and in-vivo cytotoxicity in MM cells. Finally, our mouse model with concurrent loss of the histone demethylase Utx and the activating mutation of Braf V600E in post germinal center B cells demonstrates mature B-cell malignancies including plasma cell neoplasms. Our ongoing analyses will reveal the pathogenesis of MM induced by somatic mutations, and this model is a useful tool for the development of novel molecular-targeted therapies for MM patients."

Journal • Gene Therapies • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • BMI1 • BRAF • EZH2 • MYC • NR4A1

TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations (clinicaltrials.gov) - P2; N=96; Not yet recruiting; Sponsor: Taiho Oncology, Inc.

Clinical • New P2 trial • Oncology • Solid Tumor • PTEN

TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations (clinicaltrials.gov) - P2; N=96; Recruiting; Sponsor: Taiho Oncology, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Oncology • Solid Tumor • PTEN

A Phase 2 Study of TAS-117 in Patients with Advanced Solid Tumors Harboring Germline PTEN Inactivating Mutations (clinicaltrialsregister.eu) - P2; N=100; Sponsor: Taiho Oncology, Inc.

Clinical • New P2 trial • Oncology • Solid Tumor • PTEN

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. (PubMed, Invest New Drugs) - P2 | "TAS-117 showed limited antitumor activity and manageable toxicity. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations and in patients with breast cancer harboring PIK3CA H1047R and Akt1 mutations.Trial registration: This study was retrospectively registered with ClinicalTrial.gov (NCT03017521 on January 11, 2017)."

Journal • P2 data • Preclinical • Anorexia • Breast Cancer • Diabetes • Gallbladder Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Ovarian Cancer • Solid Tumor • Thymoma • Thymus Cancer • AKT1 • PIK3CA

K-BASKET, TAS-117, PI3K/AKT Gene Aberration (clinicaltrials.gov) - P2; N=13; Completed; Sponsor: Yonsei University; Recruiting ➔ Completed; N=30 ➔ 13; Trial completion date: Dec 2020 ➔ Dec 2019

Biomarker • Enrollment change • Pan Tumor • Trial completion • Trial completion date • Oncology • Solid Tumor

Taiho Oncology to present data on futibatinib (TAS-120) at the AACR Annual Meeting 2020 (PRNewswire) - "Taiho Oncology, Inc. today announced that preclinical data for futibatinib (TAS-120) will be presented online during the American Association for Cancer Research (AACR) Virtual Annual Meeting II 2020 from June 22-24."

Preclinical • Oncology

[VIRTUAL] Synergistic antitumor activity of futibatinib, an FGFR1-4 inhibitor, and TAS-117, a selective AKT inhibitor, in FGFR-deregulated cancer models (AACR-II 2020) - "Our findings suggest that futibatinib plus TAS-117 has synergistic antitumor effects in FGFR-aberrant tumors. A phase 1/2 study of this combination in advanced solid tumors (JapicCTI-194864) is ongoing."

Preclinical • Endometrial Cancer • Gynecologic Cancers • Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • FGF • FGFR1 • FGFR2

Akt Inhibition Synergizes with PRC2 Inhibition in the Treatment of Multiple Myeloma. (PubMed, Cancer Sci) - "Consistent with these results, the dual EZH2/EZH1 inhibitor, UNC1999, but not the selective EZH2 inhibitor, GSK126, synergistically enhanced TAS-117-induced cytotoxicity and provoked myeloma cell apoptosis. Moreover, FOXO3 knockdown repressed EZH1 expression. Collectively, the present results unravel some molecular interactions between Akt signaling and epigenetic modulators, which emphasize the benefits of targeting PRC2 full activity and the Akt pathway as a therapeutic option for multiple myeloma."

Journal

Akt Inhibition Differently Controls PRC2 Components and Synergizes with Dual EZH2/1 Inhibitor in the Treatment of Multiple Myeloma (ASH 2019) - "This prompted us to examine the impact of TAS-117 combination with either dual EZH2/1 inhibitor, UNC1999, or selective EZH2 inhibitor, GSK126. In conclusion, the present results defined novel signaling-epigenetic crosstalk between PI3K/Akt pathway and PRC2 components, EZH2 and EZH1, and demonstrated that Akt inhibition can differently modulates EZH2 and EZH1 levels via Akt downstream effectors, E2F1 and FOXO3, respectively. Therefore, targeting both EZH2 and EZH1 in addition to Akt inhibition may be a promising rationale to eradicate MM, leading to significant advances in treatment."

CD8 • CDKN1B • E2F1 • EZH2 • FOXO3 • PTEN

First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumours (ESMO 2019) - "TAS-117 had a manageable safety profile with clinical antitumor activity in pts with advanced solid tumors. Further investigation of the drug in a combination therapy is in preparation. Clinical trial identification: JapicCTI-152780."

Clinical • P1 data