Clinical trial NCT04509596: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer Metastatic
Lead sponsor: Dizal Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-08-12
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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


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.

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: up to approximately 1 year
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: 21 days after the first multiple dose
measure: To define maximum tolerated dose (MTD) of DZD1516 if possible (Part A only)
timeFrame: 21 days after the first multiple dose
measure: To define Recommended Phase II Combination Dose (RP2CD) of DZD1516 in combination with trastuzumab and capecitabine (Part B only)
timeFrame: 21 days after the first multiple dose
measure: To define Recommended Phase II Combination Dose (RP2CD) of DZD1516 in combination with T-DM1 (Part C only)
timeFrame: 21 days after the first multiple dose
Secondary outcomes:
measure: Drug concentrations of DZD1516 and its metabolite DZ2678 in plasma, urine and CSF
timeFrame: up to approximately 6 months
measure: Maximum plasma concentration (Cmax) of DZD1516 and its metabolite DZ2678
timeFrame: up to approximately 6 months
measure: Area under the plasma concentration-time curve (AUC) of DZD1516 and its metabolite DZ2678
timeFrame: up to approximately 6 months
measure: Plasma concentration of capecitabine and metabolites 5-FU (Part B only)
timeFrame: up to approximately 6 months
measure: Plasma Cmax of capecitabine and 5-FU (Part B only)
timeFrame: up to approximately 6 months
measure: Plasma AUC of capecitabine and 5-FU (Part B only)
timeFrame: up to approximately 6 months
measure: Plasma concentration of DM1 (Part C only)
timeFrame: up to approximately 6 months
measure: Objective Response Rate (ORR)
timeFrame: up to approximately 1 year
measure: Disease Control Rate (DCR)
timeFrame: up to approximately 1 year
measure: Duration of Response (DoR)
timeFrame: up to approximately 1 year
measure: Progression free survival (PFS) (Part B and Part C on)
timeFrame: up to approximately 1 year
measure: Overall survival (for patients with leptomeningeal metastasis in Part B and Part C only)
timeFrame: up to approximately 1 year
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology Parkside
state: California
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Shanghai
country: China
facility: Cancer Hospital, Fudan University
Study officials:
affiliation: UCLA Hematology/Oncology Parkside
name: McAndrew
role: PRINCIPAL_INVESTIGATOR
References: