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

NCT04770246 | Terminated Phase 1 FDA Drug

• 2 other identifiers: TAS-117-2012020-004770-22
• Study Type: interventional
• Target: 17
• Locations: 4 countries
• Sites: 8

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.

Conditions

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

Keywords

TAS-117; AKT inhibitor; Allosteric inhibitor; Advanced solid tumor; Metastatic solid tumor; PTEN; Germline PTEN; Inactivating mutation; Adolescent patients; Adult patients

Outcome Measures

Primary Outcomes (3)

• 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

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

  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.

  Approximately 6 months

Secondary Outcomes (10)

• Incidence of treatment-emergent adverse events (safety) in Part B

  Approximately 7 months

• Disease Control Rate (DCR)

  Approximately 6 months

• Duration of Response (DOR)

  Approximately 6 months

• Progression Free Survival (PFS)

  Approximately 6 months

• Overall Survival (OS)

  Approximately 12 months

Study Arms (4)

TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in)

EXPERIMENTAL

Advanced or metastatic solid tumors irrespective of gene alterations

Drug: TAS-117

TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in)

EXPERIMENTAL

Advanced or metastatic solid tumors irrespective of gene alterations

Drug: TAS-117

TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in)

EXPERIMENTAL

Advanced or metastatic solid tumors with germline PTEN inactivating mutations

Drug: TAS-117

TAS-117 Phase 2 (Part B)

EXPERIMENTAL

Advanced or metastatic solid tumors with germline PTEN inactivating mutations

Drug: TAS-117

Interventions

TAS-117 DRUG

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

TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Dose Escalation in Part A
• ≥18 years of age.
• Histologically or cytologically confirmed advanced or metastatic solid tumors
• Has progressed after standard treatment for advanced or metastatic disease or was intolerant to or ineligible for available standard therapies.
• Patients with solid tumors irrespective of gene alterations.
• Patients with at least one measurable or non-measurable lesion per RECIST1.1
• Dose and Regimen Confirmation in Part A and Phase 2 (Part B)
• ≥12 years of age. Patients age ≥12 and \<18 years must have a body weight of ≥40 kg.
• Histologically confirmed advanced or metastatic solid tumors.
• Has progressed after standard treatment for advanced or metastatic disease or was intolerant or ineligible to available standard therapies.
• Patients with locally confirmed germline PTEN inactivating mutations determined from a blood sample.
• Patients with at least one measurable lesion per RECIST 1.1.

You may not qualify if:

• History or current evidence of interstitial lung disease that requires steroid medication.
• Current evidence of diabetes mellitus that requires insulin therapy.
• Prior treatment with PI3K/AKT/mTOR pathway inhibitors.
• Patients with primary brain tumor.
• Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastasis.
• Currently receiving chronic corticosteroid therapy of ≥10 mg/day of prednisone or its equivalent.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (8)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic Lerner Research Institute

Cleveland, Ohio, 44195, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Institut Gustave Roussy

Villejuif, Île-de-France Region, 98405, France

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

Related Publications (1)

• Rodon J, Funchain P, Laetsch TW, Arkenau HT, Hervieu A, Singer CF, Murciano-Goroff YR, Chawla SP, Anthony K, Yamamiya I, Liu M, Halim AB, Benhadji KA, Takahashi O, Delaloge S. A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations. Future Oncol. 2022 Sep;18(30):3377-3387. doi: 10.2217/fon-2022-0305. Epub 2022 Aug 30.

  PMID: 36039910 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

3-amino-1-methyl-3-(4-(3-phenyl-5H- imidazo(1,2-c)pyrido(3,4-e)(1,3)oxazin-2-yl)phenyl)cyclobutanol

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: February 25, 2021
• Study Start: March 31, 2021
• Primary Completion: February 28, 2023
• Study Completion: March 6, 2023
• Last Updated: September 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); GB (1); US (5); AU (1)