Found 1 Presentation For Request "467p"
467P - Dose escalation of TAS-117 in patients with advanced solid tumors
- Jordi Rodon (Houston, United States of America)
Abstract
Background
TAS-117, a non–ATP-competitive allosteric AKT inhibitor, was previously explored in a Japanese phase I study. We report preliminary results in a phase II study (NCT04770246) of TAS-117 in Western patients (pts) with advanced solid tumors harboring germline
Methods
In the dose escalation portion of this open-label, single-arm, 2-part study, the primary objectives were to evaluate safety/tolerability and determine maximum tolerated dose/recommended phase II dose (RP2D). Pts had advanced/metastatic solid tumors with germline
Results
Eligible pts (N=16; median age, 54 y; range, 23–82 y) received either the QD (n=9; 16 mg, n=3 and 20 mg, n=6) or ID (n=7; 24 mg, n=4 and 28 mg, n=3). Dose-limiting toxicities were observed (n=3): 1 at 20 mg QD (febrile neutropenia) and 2 at 28 mg ID (grade 3 oral mucositis). Twelve pts (75%) had treatment-related adverse events (TRAEs; none grade 5). The most frequent TRAEs (>10%) were rash (56%), fatigue (38%), hyperglycemia, pruritus (31%), diarrhea, stomatitis, decreased appetite (19%), nausea, hypophosphatemia, dry skin, and maculopapular rash (13%). Grade 3–4 serious TRAEs were neutropenic infection, hyperglycemia, and type 2 diabetes (6%). Unconfirmed partial response was observed in 1 pt with breast cancer; 6 pts had stable disease. A pt with breast cancer had stable disease of >8 months associated with a target lesion tumor shrinkage of ≈15%. Approximate dose-proportional exposure increase was observed within the studied dose range. Preliminary PD analysis showed pAKT decrease >50% in 7 of 8 pts and pPRAS decrease >50% in 5 of 7 pts. RP2D was defined as 16 mg QD.
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 trial identification
NCT04770246.
Editorial acknowledgement
Professional medical writing and editorial assistance were provided by Tracy Diaz, PhD, and Jennifer Robertson, PhD, at Ashfield MedComms, an Ashfield Health company, and funded by Taiho Oncology, Inc.
Legal entity responsible for the study
Taiho Oncology, Inc.
Funding
Taiho Oncology, Inc.
Disclosure
J. Rodon: Financial Interests, Personal, Advisory Board: Peptomyc, Kelun Pharmaceuticals/Klus Pharma, Ellipses Pharma, Molecular Partners, IONCTURA SA; Financial Interests, Institutional, Other, Clinical Research: Bayer, Novartis, Spectrum Pharmaceuticals, Symphogen, BioAlta, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GlaxoSmithKline; Financial Interests, Institutional, Other, Research Funding: Blueprint Medicines, Black Diamond, Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Research Funding/Clinical Research: Hummingbird, Yingli; Financial Interests, Institutional, Research Grant, Research Funding: Vall d'Hebron Institute of Oncology/Cancer Core Europe; Financial Interests, Institutional, Research Grant, Clinical Research: Bicycle Therapeutics, Taiho, Roche Pharmaceuticals, Merus, Curis, AadiBioscience, Nuvation, ForeBio, BioMed Valley Discoveries, Loxo Oncology, Hutchinson MediPharma, Cellestia, Deciphera, Ideaya, Amgen, Tango Therapeutics, Mirati, Linnaeus Therapeutics; Other, Other: VHIO/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, Boxer Capital, LLC, Tang Advisors, LLC; Other, Travel Reimbursement: European Society for Medical Oncology. H. Arkenau: Financial Interests, Personal, Invited Speaker: Servier, Guardant; Financial Interests, Personal, Advisory Board: iOnctura, Beigene; Financial Interests, Institutional, Invited Speaker: multiple small and large Pharma/Biotechs. L. Gao, M. Liu, A. Halim, M. Mina, O. Takahashi, K. Benhadji: Financial Interests, Personal, Full or part-time Employment: Taiho. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre fabre, Orion, Sanofi, Rappta, Cellectis, Isis/servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, AstraZeneca, Orion, Sanofi, Pfizer; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. All other authors have declared no conflicts of interest.