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

Phase 1

Terminated

• Conditions: Advanced Solid Tumors With HER2 Abnormalities; Advanced Solid Tumors With HER3 Abnormalities
• Interventions: Drug: TAS0728

• Registration Number: NCT03410927
• Lead Sponsor: Taiho Oncology, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-19
• Study First Submitted QC: 2018-01-19
• Study First Posted: 2018-01-25
• Study Start: 2018-04-06
• Primary Completion: 2022-06-09
• Study Completion: 2022-06-09
• Status Verified: 2022-11
• Last Update Submitted: 2024-06-25
• Last Update Posted: 2024-06-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
TAS0728	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)

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Phase 1 and 2)	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.
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.	21-day cycles
Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Phase2)	3 years

Secondary Outcome Measures

Name	Time	Method
Duration of response (phase 1 and 2)	3 years
Maximum Plasma Concentration (Cmax) after administration of TAS0728 (Phase 1)	21 days in Cycle 1
Overall survival (phase 1 and 2)	3 years
Area under the plasma drug concentration-time curve (AUC) after administration of TAS0728 (Phase 1)	21 days in Cycle 1
Disease Control Rate using RECIST 1.1 (phase 1 and 2)	3 years
Progression free survival (phase 1 and 2)	3 years

Trial Locations

Locations (8)

University of Texas - MD Anderson; 🇺🇸 Houston, Texas, United States

Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Sarah Cannon; 🇺🇸 Nashville, Tennessee, United States

Institut de Cancerologie Gustavo Roussy; 🇫🇷 Paris, France

Hospital Vall D'hebron; 🇪🇸 Barcelona, Spain

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Sarah Cannon Research Institute - UK; 🇬🇧 London, United Kingdom