A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations
Jordi Rodón1, Pauline Funchain2, Theodore W Laetsch3
1Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
PTEN acts as a potent tumor suppressor within the PI3K/AKT/mTOR pathway. Germline mutations in the PTEN gene are a hallmark of PTEN hamartoma tumor syndrome, which includes Cowden syndrome, where they appear to elevate lifetime risk of cancer. Targeted AKT directed therapy has been proposed as an effective approach in cancer patients having germline PTEN mutations. 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.
Insights
This study investigates TAS-117, an AKT inhibitor, for advanced solid tumors with germline PTEN mutations. It evaluates safety, tolerability, and antitumor activity in a phase II trial.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- PTEN is a crucial tumor suppressor in the PI3K/AKT/mTOR pathway.
- Germline PTEN mutations are linked to PTEN hamartoma tumor syndrome and increased cancer risk.
- AKT-targeted therapy is a potential strategy for cancers with germline PTEN mutations.
Purpose of the Study:
- To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of TAS-117.
- To assess the efficacy of the novel allosteric AKT inhibitor TAS-117.
- To explore TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations.
Main Methods:
- An international, two-part phase II study protocol.
- Evaluation of safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity.
- Inclusion of patients with advanced solid tumors and germline PTEN-inactivating mutations.
Main Results:
- Phase I study in Japan showed activity against certain tumor types.
- Exploration of mechanism of action, safety, and dosing regimen of TAS-117.
- Further activity and safety data to be gathered in the ongoing phase II study.
Conclusions:
- TAS-117 is a novel allosteric AKT inhibitor with potential in treating PTEN-mutated cancers.
- The phase II study will provide critical data on TAS-117's efficacy and safety.
- Targeted therapy for germline PTEN mutations represents a promising avenue in oncology.
