- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04509596
DZD1516 in Combination With Trastuzumab and Capecitabine, or in Combination With T-DM1, in Patients With Metastatic HER2 Positive Breast Cancer
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
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Hangzhou, China
- Zhejiang Cancer hospital
-
Shanghai, China
- Cancer Hospital, FuDan University
-
-
-
-
California
-
Santa Monica, California, United States, 90404
- UCLA Hematology/Oncology Parkside
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: daily dose of DZD1516
|
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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: up to approximately 1 year
|
To investigate the safety and tolerability of DZD1516
|
up to approximately 1 year
|
Incidence of dose limiting toxicities (DLTs)
Time Frame: 21 days after the first multiple dose
|
To investigate the safety and tolerability of DZD1516
|
21 days after the first multiple dose
|
To define maximum tolerated dose (MTD) of DZD1516 if possible (Part A only)
Time Frame: 21 days after the first multiple dose
|
To investigate the safety and tolerability of DZD1516
|
21 days after the first multiple dose
|
To define Recommended Phase II Combination Dose (RP2CD) of DZD1516 in combination with trastuzumab and capecitabine (Part B only)
Time Frame: 21 days after the first multiple dose
|
To investigate the safety and tolerability of DZD1516 in combination with either trastuzumab, capecitabine, or both trastuzumab and capecitabine
|
21 days after the first multiple dose
|
To define Recommended Phase II Combination Dose (RP2CD) of DZD1516 in combination with T-DM1 (Part C only)
Time Frame: 21 days after the first multiple dose
|
To investigate the safety and tolerability of DZD1516 in combination with T-DM1
|
21 days after the first multiple dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Drug concentrations of DZD1516 and its metabolite DZ2678 in plasma, urine and CSF
Time Frame: up to approximately 6 months
|
Pharmacokinetics endpoints
|
up to approximately 6 months
|
Maximum plasma concentration (Cmax) of DZD1516 and its metabolite DZ2678
Time Frame: up to approximately 6 months
|
Pharmacokinetics endpoints
|
up to approximately 6 months
|
Area under the plasma concentration-time curve (AUC) of DZD1516 and its metabolite DZ2678
Time Frame: up to approximately 6 months
|
Pharmacokinetics endpoints
|
up to approximately 6 months
|
Plasma concentration of capecitabine and metabolites 5-FU (Part B only)
Time Frame: up to approximately 6 months
|
Pharmacokinetics endpoints
|
up to approximately 6 months
|
Plasma Cmax of capecitabine and 5-FU (Part B only)
Time Frame: up to approximately 6 months
|
Pharmacokinetics endpoints
|
up to approximately 6 months
|
Plasma AUC of capecitabine and 5-FU (Part B only)
Time Frame: up to approximately 6 months
|
Pharmacokinetics endpoints
|
up to approximately 6 months
|
Plasma concentration of DM1 (Part C only)
Time Frame: up to approximately 6 months
|
Pharmacokinetics endpoints
|
up to approximately 6 months
|
Objective Response Rate (ORR)
Time Frame: up to approximately 1 year
|
To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy
|
up to approximately 1 year
|
Disease Control Rate (DCR)
Time Frame: up to approximately 1 year
|
To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy
|
up to approximately 1 year
|
Duration of Response (DoR)
Time Frame: up to approximately 1 year
|
To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy
|
up to approximately 1 year
|
Progression free survival (PFS) (Part B and Part C on)
Time Frame: up to approximately 1 year
|
To assess preliminary anti-tumor efficacy of DZD1516 as combination therapy
|
up to approximately 1 year
|
Overall survival (for patients with leptomeningeal metastasis in Part B and Part C only)
Time Frame: up to approximately 1 year
|
To assess preliminary anti-tumor efficacy of DZD1516 as combination therapy
|
up to approximately 1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: McAndrew, UCLA Hematology/Oncology Parkside
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DZ2019HE001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer Metastatic
-
Gilead SciencesRecruitingStudy of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors (ASCENT-J02)Advanced Solid Tumor | Metastatic Urothelial Cancer | Metastatic Triple-Negative Breast Cancer | HR+/HER2- Metastatic Breast CancerJapan
-
BriaCell Therapeutics CorporationRecruitingBreast Cancer | Breast Neoplasm | Metastatic Breast Cancer | Breast Cancer Metastatic | End Stage CancerUnited States
-
GlycoMimetics IncorporatedTerminatedBreast Cancer | Breast Cancer Metastatic | HR+ Metastatic Breast CancerUnited States
-
OBI Pharma, IncCompletedMetastatic Colorectal Cancer | Metastatic Lung Cancer | Metastatic Breast Cancer | Metastatic Gastric CancerTaiwan
-
Massachusetts General HospitalPuma Biotechnology, Inc.; Celcuity, Inc.WithdrawnMetastatic Breast Cancer | Invasive Breast Cancer | HER2-negative Breast Cancer | ER Positive Breast Cancer | PR-Positive Breast Cancer | Stage IV (Metastatic) Breast CancerUnited States
-
Institut de Recherches Internationales ServierADIR, a Servier Group companyCompletedMetastatic Breast Cancer | Metastatic Triple Negative Breast CancerJapan, Belgium, France, Netherlands
-
BriaCell Therapeutics CorporationLumaBridgeEnrolling by invitationBreast Cancer | Breast Neoplasm | Metastatic Breast Cancer | Breast Cancer MetastaticUnited States
-
Novartis PharmaceuticalsCompletedMetastatic Breast Cancer | Postmenopausal Women | Locally Advanced Metastatic Breast CancerIsrael
-
Hoffmann-La RocheCompletedHER2-Positive Metastatic Breast Cancer | HER2-Negative Metastatic Breast Cancer | Locally Advanced or Early Breast CancerUnited States
-
Prof. Wolfgang JanniEli Lilly and CompanyRecruitingHormone Receptor-positive Metastatic Breast Cancer | HER2-negative Metastatic Breast CancerGermany, Switzerland
Clinical Trials on 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
-
AstraZenecaActive, not recruitingAdvanced Non Small Cell Lung CancerCanada, Poland, Taiwan, United States, Korea, Republic of, Japan, Russian Federation, Ukraine
-
1ST Biotherapeutics, Inc.Merck Sharp & Dohme LLCRecruitingAdvanced Solid TumorUnited States
-
University of UlmCompletedCOVID-19 | Critically Ill | Outcome, Fatal | Interleukin 6 | TocilizumabGermany
-
Ye XuUnknownResected Liver Metastases From Colorectal CancerChina
-
Supplement Formulators, Inc.CompletedIncrease in Blood Levels of Nicotinamide Adenine Dinucleotide (NAD+)United States
-
Thrombosis Research InstituteCompletedGastric Cancer | Gastroesophageal CancerIndia
-
ANRS, Emerging Infectious DiseasesNot yet recruiting
-
Memorial Sloan Kettering Cancer CenterCompletedThyroid Cancer | Papillary MicrocarcinomaUnited States
-
OHSU Knight Cancer InstituteGenentech, Inc.; Oregon Health and Science UniversityWithdrawnAnatomic Stage III Breast Cancer AJCC v8 | Recurrent Ovarian Carcinoma | Anatomic Stage IV Breast Cancer AJCC v8 | Advanced Malignant Solid Neoplasm | Advanced Pancreatic Carcinoma | Stage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Stage IV Pancreatic Cancer AJCC v8 | Recurrent... and other conditionsUnited States
-
Julio RamirezUniversity of LouisvilleTerminatedOsteomyelitisUnited States