Advanced Solid Tumors With HER2 AbnormalitiesPhase 1NCT03410927
A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities
A Phase 1 study testing TAS0728 in people with Advanced Solid Tumors With HER2 Abnormalities and Advanced Solid Tumors With HER3 Abnormalities, run by Taiho Oncology, Inc. at 8 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors With HER2 Abnormalities, Advanced Solid Tumors With HER3 Abnormalities
- What is being tested?
- TAS0728
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 6 Apr 2018to 9 Jun 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or females with an age ≥ 18 years.
- 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
- For Phase 1, only subjects HER2 or HER3 molecular/genetic alterations will be enrolled.
- For Phase 2a, subjects with one of the following tumor types will be enrolled:
- 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).
- At least 1 measurable lesion for solid tumor
Show all 9Show fewer
- Is able to take medications orally (e.g., no feeding tube).
- Able to agree to and sign informed consent and to comply with the protocol
- Has adequate organ function
Who cannot join
- Has a serious illness or medical condition(s)
- Has received treatment with any proscribed treatments within specified time frames prior to study drug administration
- Impaired cardiac function or clinically significant cardiac disease
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States5 sites
Winship Cancer Institute
Atlanta, Georgia, 30322
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
University of Texas - MD Anderson
Houston, Texas, 77030
Sarah Cannon
Nashville, Tennessee, 37203
Icahn School of Medicine at Mount Sinai
New York, New York, 10029-6504
United Kingdom1 site
Sarah Cannon Research Institute - UK
London, W1G 6AD
About this study
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
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.
- Conditions
- Advanced Solid Tumors With HER2 Abnormalities, Advanced Solid Tumors With HER3 Abnormalities
- Being tested
- TAS0728
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAS0728Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| TAS0728 | Experimental | 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) Receives: Drug: TAS0728 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 21-day cycles
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Phase 1 and 2)
Measured: 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)
Measured: 3 years
Secondary outcomes (6)
Maximum Plasma Concentration (Cmax) after administration of TAS0728 (Phase 1)
Measured: 21 days in Cycle 1
Area under the plasma drug concentration-time curve (AUC) after administration of TAS0728 (Phase 1)
Measured: 21 days in Cycle 1
Disease Control Rate using RECIST 1.1 (phase 1 and 2)
Measured: 3 years
Progression free survival (phase 1 and 2)
Measured: 3 years
Duration of response (phase 1 and 2)
Measured: 3 years
Overall survival (phase 1 and 2)
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2018
- Study start6 Apr 2018
- Primary completion9 Jun 2022
- Study completion9 Jun 2022
Why it stopped: 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
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid Tumors With HER2 AbnormalitiesStudies of the same condition, open and under way.
- More trials run by Taiho Oncology, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- In Phase 1, TAS0728 will be evaluated for safety and tolerability, and in phase 2 will be evaluated preliminary efficacy.
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taiho Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03410927
- Sponsor's protocol ID
- TO-TAS0728-101
- Other IDs
- 2017-004415-39, 2017
- Status last verified
- Aug 2024
- First submitted
- 19 Jan 2018
- Last updated
- 5 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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 33774767Irie 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03410927
- Acronym / sponsor ID
- TO-TAS0728-101
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 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
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Taiho Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Apr 2018 (actual)
- Primary completion
- 9 Jun 2022 (actual)
- Study completion
- 9 Jun 2022 (actual)
- First posted
- 25 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- In Phase 1, TAS0728 will be evaluated for safety and tolerability, and in phase 2 will be evaluated preliminary efficacy.
| Arm | Type | Receives |
|---|---|---|
| TAS0728 | Experimental | Drug: TAS0728Group 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or females with an age ≥ 18 years.
- 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
- At least 1 measurable lesion for solid tumor
- Is able to take medications orally (e.g., no feeding tube).
- Able to agree to and sign informed consent and to comply with the protocol
Key exclusion criteria (3 listed)
- Has a serious illness or medical condition(s)
- Has received treatment with any proscribed treatments within specified time frames prior to study drug administration
- Impaired cardiac function or clinically significant cardiac disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAS0728TAS0728 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. | Drug | TAS0728 |
Primary outcome
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
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.
Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Phase2)
Time frame: 3 years
6 secondary outcomes
Maximum Plasma Concentration (Cmax) after administration of TAS0728 (Phase 1)
Time frame: 21 days in Cycle 1
Area under the plasma drug concentration-time curve (AUC) after administration of TAS0728 (Phase 1)
Time frame: 21 days in Cycle 1
Disease Control Rate using RECIST 1.1 (phase 1 and 2)
Time frame: 3 years
Progression free survival (phase 1 and 2)
Time frame: 3 years
Duration of response (phase 1 and 2)
Time frame: 3 years
Overall survival (phase 1 and 2)
Time frame: 3 years
Results and safety
The study was stopped early (reason given: 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). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
- Derived from this study: PubMed 33774767Piha-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.
- Derived from this study: PubMed 30787176Irie 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAS0728 in people with Advanced Solid Tumors With HER2 Abnormalities and Advanced Solid Tumors With HER3 Abnormalities, run by Taiho Oncology, Inc. at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, France, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: 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). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 21-day cycles). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03410927, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2024.