Clinical Trials /

TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations

NCT04770246

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
TAS-117TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in)
TAS-117TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in)
TAS-117TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in)
TAS-117TAS-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 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 patients with advanced or metastatic
           solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating
           mutations

        -  Part B (Phase 2): approximately 54 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

NameTypeDescriptionInterventions
TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in)ExperimentalAdvanced or metastatic solid tumors irrespective of gene alterations
  • TAS-117
TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in)ExperimentalAdvanced or metastatic solid tumors irrespective of gene alterations
  • TAS-117
TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in)ExperimentalAdvanced or metastatic solid tumors with germline PTEN inactivating mutations
  • TAS-117
TAS-117 Phase 2 (Part B)ExperimentalAdvanced or metastatic solid tumors with germline PTEN inactivating mutations
  • TAS-117

Eligibility Criteria

        Inclusion Criteria

          1. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          2. Dose Escalation in Part A

               1. Histologically or cytologically confirmed advanced or metastatic solid tumors

               2. Has progressed after standard treatment for advanced or metastatic disease or was
                  intolerant to or ineligible for available standard therapies.

               3. Patients with solid tumors irrespective of gene alterations.

               4. 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. Histologically confirmed advanced or metastatic solid tumors.

               2. Has progressed after standard treatment for advanced or metastatic disease or was
                  intolerant or ineligible to available standard therapies.

               3. Patients with locally confirmed germline PTEN inactivating mutations determined
                  from a blood sample.

               4. 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:18 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

Last Updated

March 4, 2021