Clinical Trials /

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

NCT04509596

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: DZ2019HE001
  • NCT ID: NCT04509596

Conditions

  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
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 Cdaily dose of DZD1516

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
daily dose of DZD1516Experimentaldaily dose of DZD1516
  • 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

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame:up to approximately 1 year
Safety Issue:
Description:To investigate the safety and tolerability of DZD1516

Secondary Outcome Measures

Measure:Drug concentrations of DZD1516 and its metabolite DZ2678 in plasma, urine and CSF
Time Frame:up to approximately 6 months
Safety Issue:
Description:Pharmacokinetics endpoints
Measure:Maximum plasma concentration (Cmax) of DZD1516 and its metabolite DZ2678
Time Frame:up to approximately 6 months
Safety Issue:
Description:Pharmacokinetics endpoints
Measure:Area under the plasma concentration-time curve (AUC) of DZD1516 and its metabolite DZ2678
Time Frame:up to approximately 6 months
Safety Issue:
Description:Pharmacokinetics endpoints
Measure:Plasma concentration of capecitabine and metabolites 5-FU (Part B only)
Time Frame:up to approximately 6 months
Safety Issue:
Description:Pharmacokinetics endpoints
Measure:Plasma Cmax of capecitabine and 5-FU (Part B only)
Time Frame:up to approximately 6 months
Safety Issue:
Description:Pharmacokinetics endpoints
Measure:Plasma AUC of capecitabine and 5-FU (Part B only)
Time Frame:up to approximately 6 months
Safety Issue:
Description:Pharmacokinetics endpoints
Measure:Plasma concentration of DM1 (Part C only)
Time Frame:up to approximately 6 months
Safety Issue:
Description:Pharmacokinetics endpoints
Measure:Objective Response Rate (ORR)
Time Frame:up to approximately 1 year
Safety Issue:
Description:To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy
Measure:Disease Control Rate (DCR)
Time Frame:up to approximately 1 year
Safety Issue:
Description:To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy
Measure:Duration of Response (DoR)
Time Frame:up to approximately 1 year
Safety Issue:
Description:To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy
Measure:Progression free survival (PFS) (Part B and Part C on)
Time Frame:up to approximately 1 year
Safety Issue:
Description:To assess preliminary anti-tumor efficacy of DZD1516 as combination therapy
Measure:Overall survival (for patients with leptomeningeal metastasis in Part B and Part C only)
Time Frame:up to approximately 1 year
Safety Issue:
Description:To assess preliminary anti-tumor efficacy of DZD1516 as combination therapy

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dizal Pharmaceuticals

Last Updated

August 10, 2020