Description:
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.
Title
- Brief Title: TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations
- Official Title: A Phase 2 Study of TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Inactivating Mutations
Clinical Trial IDs
- ORG STUDY ID:
TAS-117-201
- SECONDARY ID:
2020-004770-22
- NCT ID:
NCT04770246
Conditions
- Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations
- Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations
Interventions
Drug | Synonyms | Arms |
---|
TAS-117 | | TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in) |
TAS-117 | | TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in) |
TAS-117 | | TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in) |
TAS-117 | | TAS-117 Phase 2 (Part B) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in) | Experimental | Advanced or metastatic solid tumors irrespective of gene alterations | |
TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in) | Experimental | Advanced or metastatic solid tumors irrespective of gene alterations | |
TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in) | Experimental | Advanced or metastatic solid tumors with germline PTEN inactivating mutations | |
TAS-117 Phase 2 (Part B) | Experimental | Advanced or metastatic solid tumors with germline PTEN inactivating mutations | |
Eligibility Criteria
Inclusion Criteria
1. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
2. Dose Escalation in Part A
1. ≥18 years of age.
2. Histologically or cytologically confirmed advanced or metastatic solid tumors
3. Has progressed after standard treatment for advanced or metastatic disease or was
intolerant to or ineligible for available standard therapies.
4. Patients with solid tumors irrespective of gene alterations.
5. Patients with at least one measurable or non-measurable lesion per RECIST1.1
3. Dose and Regimen Confirmation in Part A and Phase 2 (Part B)
1. ≥12 years of age. Patients age ≥12 and <18 years must have a body weight of ≥40
kg.
2. Histologically confirmed advanced or metastatic solid tumors.
3. Has progressed after standard treatment for advanced or metastatic disease or was
intolerant or ineligible to available standard therapies.
4. Patients with locally confirmed germline PTEN inactivating mutations determined
from a blood sample.
5. Patients with at least one measurable lesion per RECIST 1.1.
Exclusion Criteria
1. History or current evidence of interstitial lung disease that requires steroid
medication.
2. Current evidence of diabetes mellitus that requires insulin therapy.
3. Prior treatment with PI3K/AKT/mTOR pathway inhibitors.
4. Patients with primary brain tumor.
5. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord
compression, or symptomatic or unstable brain metastasis.
6. Currently receiving chronic corticosteroid therapy of ≥10 mg/day of prednisone or its
equivalent.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 12 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of treatment-emergent adverse events and dose-limiting toxicities (safety and tolerability) and MTD of TAS-117 in Part A |
Time Frame: | 21 days for DLT evaluation, approximately 7 months for the others |
Safety Issue: | |
Description: | Number of patients with abnormal laboratory values, treatment emergent AEs, abnormal vital signs and ECG, and Dose-limiting toxicities (DLTs) |
Secondary Outcome Measures
Measure: | Incidence of treatment-emergent adverse events (safety) in Part B |
Time Frame: | Approximately 7 months |
Safety Issue: | |
Description: | Number of patients with abnormal laboratory values, treatment-emergent AEs, abnormal vital signs and ECG |
Measure: | Disease Control Rate (DCR) |
Time Frame: | Approximately 6 months |
Safety Issue: | |
Description: | DCR, defined as the proportion of patients experiencing a best overall response of stable response (SD), PR, or complete response (CR). |
Measure: | Duration of Response (DOR) |
Time Frame: | Approximately 6 months |
Safety Issue: | |
Description: | 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. |
Measure: | Progression Free Survival (PFS) |
Time Frame: | Approximately 6 months |
Safety Issue: | |
Description: | 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. |
Measure: | Overall Survival (OS) |
Time Frame: | Approximately 12 months |
Safety Issue: | |
Description: | OS, defined as the time from the date of first dose to the death date. |
Measure: | Pharmacokinetics (PK) profile of TAS-117 in Part A |
Time Frame: | 21 days |
Safety Issue: | |
Description: | area under the plasma concentration-time curve (AUC) |
Measure: | Pharmacokinetics (PK) profile of TAS-117 in Part A |
Time Frame: | 21 days |
Safety Issue: | |
Description: | time to reach maximum plasma concentration (Tmax) |
Measure: | Pharmacokinetics (PK) profile of TAS-117 in Part A |
Time Frame: | 21 days |
Safety Issue: | |
Description: | terminal elimination half-life (T1/2) |
Measure: | Pharmacokinetics (PK) profile of TAS-117 in Part A |
Time Frame: | 21 days |
Safety Issue: | |
Description: | maximum plasma concentration (Cmax) |
Measure: | Pharmacodynamics (PD) profile of TAS-117 in Part A |
Time Frame: | 21 days |
Safety Issue: | |
Description: | Evaluate Total and Phosphorylated AKT and PRAS40 |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Taiho Oncology, Inc. |
Trial Keywords
- TAS-117
- AKT inhibitor
- Allosteric inhibitor
- Advanced solid tumor
- Metastatic solid tumor
- PTEN
- Germline PTEN
- Inactivating mutation
- Adolescent patients
- Adult patients
Last Updated
August 3, 2021