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Breast Cancer MetastaticPhase 1NCT04509596

DZD1516 in Combination With Trastuzumab and Capecitabine, or in Combination With T-DM1, in Patients With Metastatic HER2 Positive Breast Cancer

A Phase 1 study testing DZD1516 mono therapy in Part A, DZD1516 in combination with trastuzumab and/or capecitabine in Part B, DZD1516 in combination with T-DM1 in Part C in people with Breast Cancer Metastatic, run by Dizal Pharmaceuticals at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

DZD1516 is an oral, blood brain barrier penetrable, selective HER2 tyrosine kinase inhibitor. This study is designed to evaluate the safety and tolerability of DZD1516 in patients with metastatic HER2 positive breast cancer who have progressed following prior therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer Metastatic
What is being tested?
DZD1516 mono therapy in Part A, DZD1516 in combination with trastuzumab and/or capecitabine in Part B, DZD1516 in combination with T-DM1 in Part C
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
3 sitesin 2 countries
Study dates
21 Sep 2020to 7 Jul 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

  • Signed informed consent.
  • Male or female patients aged ≥ 18 years
  • histologically or cytologically confirmed HER2 positive advanced breast cancer which failed prior therapies
  • Predicted life expectancy ≥ 12 weeks.
  • ECOG performance status 0 to 1 for patients without LM, and 0 to 2 for patients with LM at the time of signing ICF
  • Adequate bone marrow reserve and organ system functions
  • For patients without CNS metastases, patients must have at least one measurable lesion according to RECIST (version 1.1)
  • For patients with Brain metastasis: Patient must have at least one measurable intracranial lesion according to modified RECIST 1.1

Who cannot join

  • Intervention with any of the following: Any investigational agents or study drugs from a previous clinical study within 4 weeks of the first dose of study treatment； Any cytotoxic chemotherapy or other anticancer drugs for the treatment of metastatic breast cancer from a previous treatment regimen within 4 weeks of the first dose of study treatment； Any intrathecal chemotherapy within 2 weeks of the first dose of study treatment；Major surgery procedure (excluding placement of vascular access), or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study； Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment;
  • CNS complications that require urgent neurosurgical intervention
  • Any evidence of severe or uncontrolled systemic diseases
  • Another malignancy within 5 years prior to enrolment with the exception of adequately treated in-situ carcinoma of the cervix, uterus, basal or squamous cell carcinoma or non-melanomatous skin cancer.
  • Live vaccines within 4 weeks prior to first dose.
  • Active infections including:Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice)；Positive Hepatitis B surface antigen (HBsAg) or positive HCV antibodies or confirmed positive HIV test result.
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  • Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of DZD1516
  • Involvement in the planning and conduct of the study (applies to Sponsor staff or staff at the study site).
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

China2 sites

  • Zhejiang Cancer Hospital

    Hangzhou

  • Cancer Hospital, Fudan University

    Shanghai

Other trials in China

United States1 site

  • UCLA Hematology/Oncology Parkside

    Santa Monica, California, 90404

Other trials in United States

About this study

Official title: A Phase I, Open-Label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of DZD1516 in Combination With Trastuzumab and Capecitabine, or DZD1516 in Combination With T-DM1, in Patients With Metastatic HER2 Positive (HER2+) Breast Cancer

DZD1516 is an oral, blood brain barrier penetrable, selective HER2 tyrosine kinase inhibitor. This study is designed to evaluate the safety and tolerability of DZD1516 in patients with metastatic HER2 positive breast cancer who have progressed following prior therapy. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body and assess its anti-cancer activity as monotherapy and in combination with trastuzumab and/or capecitabine, or in combination with T-DM1

Being tested
DZD1516 mono therapy in Part A, DZD1516 in combination with trastuzumab and/or capecitabine in Part B, DZD1516 in combination with T-DM1 in Part C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DZD1516 mono therapy in Part A, DZD1516 in combination with trastuzumab and/or capecitabine in Part B, DZD1516 in combination with T-DM1 in Part CDrug

    Part A is twice daily (except Cycle 0) oral dosing of DZD1516, starting from 50 mg. If tolerated, dose will be escalated in subsequent cohorts until MTD.

    Part B is twice daily oral dosing of DZD1516 in combination with capecitabine 1000 mg/m2 orally twice daily on Days 1-14 of each 21-day cycle or with trastuzumab 8 mg/kg intravenously (IV) on Day 1 of Cycle 1, followed by 6 mg/kg on Day 1 of each 21-day cycle.

    Part C is twice daily oral dosing of DZD1516 in combination with T-DM1 3.6 mg/kg intravenously (IV) once every 21 days

Study groups in NCT04509596
Study groupRoleWhat they receive
daily dose of DZD1516Experimentaldaily dose of DZD1516
Receives: Drug: DZD1516 mono therapy in Part A, DZD1516 in combination with trastuzumab and/or capecitabine in Part B, DZD1516 in combination with T-DM1 in Part C

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events (AEs) and serious adverse events (SAEs)

    To investigate the safety and tolerability of DZD1516

    Measured: up to approximately 1 year

  2. Incidence of dose limiting toxicities (DLTs)

    To investigate the safety and tolerability of DZD1516

    Measured: 21 days after the first multiple dose

  3. To define maximum tolerated dose (MTD) of DZD1516 if possible (Part A only)

    To investigate the safety and tolerability of DZD1516

    Measured: 21 days after the first multiple dose

  4. To define Recommended Phase II Combination Dose (RP2CD) of DZD1516 in combination with trastuzumab and capecitabine (Part B only)

    To investigate the safety and tolerability of DZD1516 in combination with either trastuzumab, capecitabine, or both trastuzumab and capecitabine

    Measured: 21 days after the first multiple dose

  5. To define Recommended Phase II Combination Dose (RP2CD) of DZD1516 in combination with T-DM1 (Part C only)

    To investigate the safety and tolerability of DZD1516 in combination with T-DM1

    Measured: 21 days after the first multiple dose

Secondary outcomes (12)

  1. Drug concentrations of DZD1516 and its metabolite DZ2678 in plasma, urine and CSF

    Pharmacokinetics endpoints

    Measured: up to approximately 6 months

  2. Maximum plasma concentration (Cmax) of DZD1516 and its metabolite DZ2678

    Pharmacokinetics endpoints

    Measured: up to approximately 6 months

  3. Area under the plasma concentration-time curve (AUC) of DZD1516 and its metabolite DZ2678

    Pharmacokinetics endpoints

    Measured: up to approximately 6 months

  4. Plasma concentration of capecitabine and metabolites 5-FU (Part B only)

    Pharmacokinetics endpoints

    Measured: up to approximately 6 months

  5. Plasma Cmax of capecitabine and 5-FU (Part B only)

    Pharmacokinetics endpoints

    Measured: up to approximately 6 months

  6. Plasma AUC of capecitabine and 5-FU (Part B only)

    Pharmacokinetics endpoints

    Measured: up to approximately 6 months

  7. Plasma concentration of DM1 (Part C only)

    Pharmacokinetics endpoints

    Measured: up to approximately 6 months

  8. Objective Response Rate (ORR)

    To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy

    Measured: up to approximately 1 year

  9. Disease Control Rate (DCR)

    To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy

    Measured: up to approximately 1 year

  10. Duration of Response (DoR)

    To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy

    Measured: up to approximately 1 year

  11. Progression free survival (PFS) (Part B and Part C on)

    To assess preliminary anti-tumor efficacy of DZD1516 as combination therapy

    Measured: up to approximately 1 year

  12. Overall survival (for patients with leptomeningeal metastasis in Part B and Part C only)

    To assess preliminary anti-tumor efficacy of DZD1516 as combination therapy

    Measured: up to approximately 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2020
  2. Study start21 Sep 2020
  3. Primary completion7 Jul 2022
  4. Study completion7 Jul 2022

Resources

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
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04509596
Sponsor's protocol ID
DZ2019HE001
Status last verified
Mar 2025
First submitted
3 Aug 2020
Last updated
1 Apr 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhang J, McAndrew NP, Wang X, Du Y, DiCarlo B, Wang M, Chen K, Yu W, Hu X. Preclinical and clinical activity of DZD1516, a full blood-brain barrier-penetrant, highly selective HER2 inhibitor. Breast Cancer Res. 2023 Jul 6;25(1):81. doi: 10.1186/s13058-023-01679-4.

    PubMed 37415239

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DZD1516 mono therapy in Part A, DZD1516 in combination with trastuzumab and/or capecitabine in Part B, DZD1516 in combination with T-DM1 in Part C in people with Breast Cancer Metastatic, run by Dizal Pharmaceuticals at 3 sites in 2 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 8 inclusion and 9 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: finished, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China, United States. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of adverse events (AEs) and serious adverse events (SAEs) (time frame: up to approximately 1 year). The study lists 5 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 NCT04509596, which also lists 1 linked publication.

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 1 Apr 2025.

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