Clinical trial NCT03410927: A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities
Official title: A Phase 1/2, Open Label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of TAS0728, an Oral Covalent Binding Inhibitor of HER2, in Subjects With Advanced Solid Tumors With HER2 or HER3 Abnormalities
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2018-01-25
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: In Phase 1, TAS0728 will be evaluated for safety and tolerability, and in phase 2 will be evaluated preliminary efficacy.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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:

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

Primary outcomes:
measure: 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.
timeFrame: 21-day cycles
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Phase 1 and 2)
timeFrame: 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.
measure: Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Phase2)
timeFrame: 3 years
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) after administration of TAS0728 (Phase 1)
timeFrame: 21 days in Cycle 1
measure: Area under the plasma drug concentration-time curve (AUC) after administration of TAS0728 (Phase 1)
timeFrame: 21 days in Cycle 1
measure: Disease Control Rate using RECIST 1.1 (phase 1 and 2)
timeFrame: 3 years
measure: Progression free survival (phase 1 and 2)
timeFrame: 3 years
measure: Duration of response (phase 1 and 2)
timeFrame: 3 years
measure: Overall survival (phase 1 and 2)
timeFrame: 3 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Nashville
country: United States
facility: Sarah Cannon
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson
state: Texas
city: Paris
country: France
facility: Institut de Cancerologie Gustavo Roussy
city: Barcelona
country: Spain
facility: Hospital Vall D'hebron
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute - UK
Study officials:
References:
citation: 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.
citation: 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.