TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations
- Conditions
- Advanced or Metastatic Solid Tumors Irrespective of Gene AlterationsAdvanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations
- Interventions
- Registration Number
- NCT04770246
- Lead Sponsor
- Taiho Oncology, Inc.
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of TAS-117 in patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations.
- Detailed Description
Study TAS-117-201 is an open-label, single-arm Phase 2 study evaluating the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of TAS-117 in patients with advanced or metastatic solid tumors harboring germline PTEN inactivating mutations. The study will be conducted in two parts:
* Part A: Safety lead-in (Dose Escalation and Dose Regimen Confirmation)
* Part B: Single-arm Phase 2 study
Patients will receive TAS-117 orally every day or intermittently on a 21-day cycle
* Part A (Dose Escalation): up to 36 adult patients with advanced or metastatic solid tumors (excluding primary brain tumors) irrespective of gene alterations. The Dose Escalation consists of 2 cohorts: Daily Dose Regimen and Intermittent Dose Regimen.
* Part A (Dose Regimen Confirmation): approximately 6 adult or adolescent patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations
* Part B (Phase 2): approximately 54 adult or adolescent patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations
Treatment will continue until disease progression, unacceptable toxicity, or any other of the criteria for treatment discontinuation is met. For patients who discontinue treatment for reasons other than disease progression, tumor assessments should be continued until radiologic disease progression is documented or until initiation of subsequent new anticancer therapy (whichever occurs first).
Patients will be followed for survival every 12 weeks (±2 weeks) until survival events (deaths) have been reported for 75% of enrolled patients or the study is terminated early by the Sponsor.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 17
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in) TAS-117 Advanced or metastatic solid tumors irrespective of gene alterations TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in) TAS-117 Advanced or metastatic solid tumors with germline PTEN inactivating mutations TAS-117 Phase 2 (Part B) TAS-117 Advanced or metastatic solid tumors with germline PTEN inactivating mutations TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in) TAS-117 Advanced or metastatic solid tumors irrespective of gene alterations
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events and dose-limiting toxicities (safety and tolerability) and MTD of TAS-117 in Part A 21 days for DLT evaluation, approximately 7 months for the others Number of patients with abnormal laboratory values, treatment emergent AEs, abnormal vital signs and ECG, and Dose-limiting toxicities (DLTs)
Objective Response Rate (ORR) in Part B (including all patients with germline PTEN mutations in Part A) Approximately 6 months ORR, defined as the proportion of patients experiencing a best overall response of CR or PR per RECIST 1.1.
Recommended Phase 2 Dose (RP2D) of TAS-117 in Part A 21 days for DLT evaluation, approximately 7 months for the others
- Secondary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (safety) in Part B Approximately 7 months Number of patients with abnormal laboratory values, treatment-emergent AEs, abnormal vital signs and ECG
Overall Survival (OS) Approximately 12 months OS, defined as the time from the date of first dose to the death date.
Disease Control Rate (DCR) Approximately 6 months DCR, defined as the proportion of patients experiencing a best overall response of stable response (SD), PR, or complete response (CR).
Progression Free Survival (PFS) Approximately 6 months PFS, defined as the time from date of the first dose of study treatment to the date of disease progression based on Investigator assessment of radiographic images or death, whichever occurs first.
Duration of Response (DOR) Approximately 6 months DOR, defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
Pharmacodynamics (PD) profile of TAS-117 in Part A 21 days Evaluate Total and Phosphorylated AKT and PRAS40
Pharmacokinetics (PK) profile of TAS-117 in Part A 21 days terminal elimination half-life (T1/2)
Trial Locations
- Locations (8)
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
Cleveland Clinic Lerner Research Institute
🇺🇸Cleveland, Ohio, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Institut Gustave Roussy
🇫🇷Villejuif, Ile De France, France
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Medical University of Vienna
🇦🇹Vienna, Austria