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

Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations Clinical Trial

Official title:

A Phase 2 Study of TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Inactivating Mutations

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04770246
• Other study ID #: TAS-117-201
• Secondary ID: 2020-004770-22
• Status: Terminated
• Phase: Phase 1
• Start date: March 31, 2021
• Est. completion date: March 6, 2023

Study information

• Verified date: October 2023
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: March 6, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations
• Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations
• Neoplasms

Intervention

Drug:
• TAS-117
TAS-117 will be dosed orally every day on a 21-day cycle
• TAS-117
TAS-117 will be dosed intermittently on a 21-day cycle
• TAS-117
TAS-117 will be dosed orally every day or intermittently on a 21-day cycle
• TAS-117
TAS-117 will be dosed orally every day or intermittently on a 21-day cycle

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
France	Institut Gustave Roussy	Villejuif	Ile De France
United Kingdom	Sarah Cannon Research Institute	London
United States	Cleveland Clinic Lerner Research Institute	Cleveland	Ohio
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Sarcoma Oncology Research Center	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Countries where clinical trial is conducted

United States,  Austria,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events and dose-limiting toxicities (safety and tolerability) and MTD of TAS-117 in Part A	Number of patients with abnormal laboratory values, treatment emergent AEs, abnormal vital signs and ECG, and Dose-limiting toxicities (DLTs)	21 days for DLT evaluation, approximately 7 months for the others
Primary	Recommended Phase 2 Dose (RP2D) of TAS-117 in Part A		21 days for DLT evaluation, approximately 7 months for the others
Primary	Objective Response Rate (ORR) in Part B (including all patients with germline PTEN mutations in Part A)	ORR, defined as the proportion of patients experiencing a best overall response of CR or PR per RECIST 1.1.	Approximately 6 months
Secondary	Incidence of treatment-emergent adverse events (safety) in Part B	Number of patients with abnormal laboratory values, treatment-emergent AEs, abnormal vital signs and ECG	Approximately 7 months
Secondary	Disease Control Rate (DCR)	DCR, defined as the proportion of patients experiencing a best overall response of stable response (SD), PR, or complete response (CR).	Approximately 6 months
Secondary	Duration of Response (DOR)	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.	Approximately 6 months
Secondary	Progression Free Survival (PFS)	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.	Approximately 6 months
Secondary	Overall Survival (OS)	OS, defined as the time from the date of first dose to the death date.	Approximately 12 months
Secondary	Pharmacokinetics (PK) profile of TAS-117 in Part A	maximum plasma concentration (Cmax)	21 days
Secondary	Pharmacokinetics (PK) profile of TAS-117 in Part A	area under the plasma concentration-time curve (AUC)	21 days
Secondary	Pharmacokinetics (PK) profile of TAS-117 in Part A	time to reach maximum plasma concentration (Tmax)	21 days
Secondary	Pharmacokinetics (PK) profile of TAS-117 in Part A	terminal elimination half-life (T1/2)	21 days
Secondary	Pharmacodynamics (PD) profile of TAS-117 in Part A	Evaluate Total and Phosphorylated AKT and PRAS40	21 days