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

Phase 1TerminatedNCT04770246

Taiho Oncology, Inc.17 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

TAS-117DRUG

TAS-117 will be dosed orally every day on a 21-day cycle

TAS-117DRUG

TAS-117 will be dosed intermittently on a 21-day cycle

TAS-117DRUG

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

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Locations (8)

Sarcoma Oncology Research Center

Santa Monica, California, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Cleveland Clinic Lerner Research Institute

Cleveland, Ohio, United States

Children's Hospital of Philadelphia

Outcomes

Primary Outcomes

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)

Time frame: 21 days for DLT evaluation, approximately 7 months for the others

Recommended Phase 2 Dose (RP2D) of TAS-117 in Part A

Time frame: 21 days for DLT evaluation, approximately 7 months for the others

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.

Time frame: Approximately 6 months

Secondary Outcomes

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

Time frame: Approximately 7 months

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).

Time frame: Approximately 6 months

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.

Time frame: Approximately 6 months

Progression Free Survival (PFS)

Data from ClinicalTrials.gov

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