Advanced Solid Tumors With HER2 Abnormalities, Advanced Solid Tumors With HER3 Abnormalities
Conditions
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
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.
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.
Sponsors
Taiho Oncology, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In Phase 1, TAS0728 will be evaluated for safety and tolerability, and in phase 2 will be evaluated preliminary efficacy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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. |
| Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Phase2) | 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival (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 |
| Duration of response (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 |
Countries
France, Spain, United Kingdom, United States
Outcome results
None listed