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TerminatedNCT03410927Updated Sep 5, 2024

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities

A Phase 1 interventional study of TAS0728 in Advanced Solid Tumors With HER2 Abnormalities and Advanced Solid Tumors With HER3 Abnormalities, sponsored by Taiho Oncology, Inc.. Terminated at 8 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-05.

Sponsored by Taiho Oncology, Inc. · Phase 1, Interventional, and Treatment

Why this study was terminated
The study was stopped due to unacceptable toxicity during the dose-escalation portion (Phase 1) of the study and did not progress to Phase 2
Phase
Phase 1
Study type
Interventional
Enrollment
19
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This is a First-in-Human (FIH), 2-part, Phase 1/2, open-label, multicenter study design to evaluate the safety, tolerability, PK, pharmacodynamics, PGx, and efficacy of TAS0728. This study consists of Phase 1 and Phase 2 components in subjects with advanced solid tumors with HER2 or HER3 overexpression, amplification, or mutation who have progressed despite standard therapy or for which no standard therapy exists, particularly urothelial cancer, biliary tract cancer, metastatic breast cancer, non-small cell lung cancer and colorectal cancer.

02

Conditions studied

  • Advanced Solid Tumors With HER2 Abnormalities
  • Advanced Solid Tumors With HER3 Abnormalities

Keywords

  • Phase I
  • solid tumors
  • pharmacokinetics
  • pharmacodynamics
  • MTD
  • TAS0728
  • HER2
  • HER3 mutation
  • amplification or overexpression
  • Urothelial cancer with HER2 or HER3 mutation
  • Biliary tract cancer with HER2 or HER3 mutation
  • MBC with HER2 amplification or overexpression or HER3 mutation
  • NSCLC with HER2 or HER3 mutation
  • CRC with HER2 or HER3 mutation
  • amplification
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or females with an age ≥ 18 years.
  2. Subjects with histological- or cytological-confirmed, advanced cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists

    1. For Phase 1, only subjects HER2 or HER3 molecular/genetic alterations will be enrolled.
    2. For Phase 2a, subjects with one of the following tumor types will be enrolled:

    i. Urothelial cancer with HER2 or HER3 mutation ii. Biliary tract cancer with HER2 or HER3 mutation iii. Breast cancer with HER2 or HER3 mutation iv. Breast cancer with HER2 amplification or overexpression v. NSCLC with HER2 or HER3 mutation vi. CRC with HER2 mutation or amplification vii. Other tumors with HER2 mutation/amplification/overexpression or HER3 mutation (gastric/GEJ, endometrial).

  3. At least 1 measurable lesion for solid tumor
  4. Is able to take medications orally (e.g., no feeding tube).
  5. Able to agree to and sign informed consent and to comply with the protocol
  6. Has adequate organ function

Exclusion criteria

Exclusion Criteria:

  1. Has a serious illness or medical condition(s)
  2. Has received treatment with any proscribed treatments within specified time frames prior to study drug administration
  3. Impaired cardiac function or clinically significant cardiac disease
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
19 participants (actual)

Study arms

  • Experimental
    TAS0728

    Group 1: Urothelial cancer with HER2 or HER3 mutation Group 2: Biliary tract cancer with HER2 or HER3 mutation Group 3: Breast cancer with HER2 or HER3 mutation Group 4: Breast cancer with HER2 amplification or overexpression as per American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) 2013 guidelines Group 5: Non-small cell lung cancer (NSCLC) with HER2 or HER3 mutation Group 6: Colorectal cancer (CRC) with HER2 mutation or amplification Group 7: Other tumors with HER2 or HER3 mutation, amplification, or overexpression (eg, gastric or gastroesophageal junction (GEJ), endometrial)

    Drug: TAS0728

Interventions

  • DrugTAS0728

    TAS0728 is an oral HER2 covalent inhibitor investigated in patients with advanced solid tumor harboring HER2 or HER3 abnormalities. It will be administered orally at a starting dose of 50 mg BID each morning and evening and escalated to the DLT. The MTD will be used for the phase 2 arms of the study.

05

What researchers measure

Primary outcomes

  1. Number of patients experiencing Dose Limiting Toxicity graded according to CTCAE Version 4.03, observed in the Cycle 1 in order to meet the objective of assessment of the MTD of TAS0728.

    Time frame: 21-day cycles

  2. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Phase 1 and 2)

    Time frame: Safety monitoring will begin at the informed consent obtained and continue up to 30 days after the last dose of TAS0728 or until new antitumor therapy, whichever is earlier.

  3. Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Phase2)

    Time frame: 3 years

Secondary outcomes

  1. Maximum Plasma Concentration (Cmax) after administration of TAS0728 (Phase 1)

    Time frame: 21 days in Cycle 1

  2. Area under the plasma drug concentration-time curve (AUC) after administration of TAS0728 (Phase 1)

    Time frame: 21 days in Cycle 1

  3. Disease Control Rate using RECIST 1.1 (phase 1 and 2)

    Time frame: 3 years

  4. Progression free survival (phase 1 and 2)

    Time frame: 3 years

  5. Duration of response (phase 1 and 2)

    Time frame: 3 years

  6. Overall survival (phase 1 and 2)

    Time frame: 3 years

06

Study locations

8 sites
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • Winship Cancer Institute
    Atlanta, Georgia 30322, United States
  • Icahn School of Medicine at Mount Sinai
    New York, New York 10029-6504, United States
  • Sarah Cannon
    Nashville, Tennessee 37203, United States
  • University of Texas - MD Anderson
    Houston, Texas 77030, United States
  • Institut de Cancerologie Gustavo Roussy
    Paris, 94800, France
  • Hospital Vall D'hebron
    Barcelona, 8035, Spain
  • Sarah Cannon Research Institute - UK
    London, W1G 6AD, United Kingdom
07

References and documents

Publications

  • Piha-Paul SA, Azaro A, Arkenau HT, Oh DY, Galsky MD, Pal SK, Hamada K, He Y, Yamamiya I, Benhadji KA, Hollebecque A. A first-in-human phase I study of TAS0728, an oral covalent binding inhibitor of HER2, in patients with advanced solid tumors with HER2 or HER3 aberrations. Invest New Drugs. 2021 Oct;39(5):1324-1334. doi: 10.1007/s10637-021-01104-7. Epub 2021 Mar 27. PubMed 33774767 ↗
  • Irie H, Ito K, Fujioka Y, Oguchi K, Fujioka A, Hashimoto A, Ohsawa H, Tanaka K, Funabashi K, Araki H, Kawai Y, Shimamura T, Wadhwa R, Ohkubo S, Matsuo K. TAS0728, A Covalent-binding, HER2-selective Kinase Inhibitor Shows Potent Antitumor Activity in Preclinical Models. Mol Cancer Ther. 2019 Apr;18(4):733-742. doi: 10.1158/1535-7163.MCT-18-1085. Epub 2019 Feb 20. PubMed 30787176 ↗
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Registry details

Key details

Study ID
NCT03410927
Lead sponsor
Taiho Oncology, Inc.
Responsible party
Sponsor
First posted
Jan 25, 2018
Start date
Apr 6, 2018
Primary completion
Jun 9, 2022
Completion
Jun 9, 2022
Last update
Sep 5, 2024

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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