Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase I, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Escalating Doses of DHES0815A in Patients With HER2-Positive Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03451162
• Other study ID #: GO39869
• Status: Completed
• Phase: Phase 1
• Start date: April 17, 2018
• Est. completion date: July 16, 2021

Study information

• Verified date: January 2022
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This first-in-human, Phase 1, open-label, multicenter, dose-escalation study will evaluate the safety, tolerability, and PK of DHES0815A as a single agent in participants with advanced and/or metastatic HER2-positive breast cancer for whom established treatment has proven ineffective or intolerable or is unavailable. The study may include a dose-expansion cohort (based on an ongoing assessment of the totality of data obtained in this study) to further assess safety, tolerability, PK, and preliminary anti-tumor activity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: July 16, 2021
• Est. primary completion date: July 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Measurable disease by RECIST v1.1 with at least one measurable target lesion
• Locally advanced or metastatic HER2-positive breast cancer that has relapsed or is refractory to established therapies
• Adequate hematologic and end-organ function
• For dose-expansion cohort only: no more than two prior systemic chemotherapy-containing regimens in the advanced/metastatic setting (excluding trastuzumab emtansine, which is considered a targeted cytotoxic agent)

Key Exclusion Criteria:

• Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 4 weeks prior to initiation of DHES0815A
• History of exposure to the protocol specified doses of anthracyclines
• Pregnancy, lactation, or breastfeeding
• Major surgical procedure within 4 weeks prior to Day 1
• Evidence of a significant uncontrolled concomitant disease of the nervous system, pulmonary, autoimmune, renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture
• Known active bacterial, viral, fungal, mycobacterial, or other infection
• Clinically significant history of liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
• Untreated or active central nervous system metastases
• Cardiopulmonary dysfunction, including inadequate left ventricular ejection function at baseline, less than 50% by either echocardiogram or multiple-gated acquisition scan
• QT interval corrected through use of Fridericia's formula (QTcF) > 470 milliseconds

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• DHES0815A
DHES0815A will be administered via intravenous (IV) infusion on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AEs) and Serious AEs		From Day 1 to end of study (up to approximately 45 months)
Primary	Percentage of Participants with DLT		From Day 1 up to Day 21
Primary	MTD of DHES0815A		From Day 1 up to Day 21
Primary	Recommended Phase 2 Dose (RP2D) of DHES0815A		From Day 1 up to Day 21
Secondary	Concentration of DHES0815A		Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)
Secondary	Area Under the Concentration-Time Curve (AUC) of DHES0815A		Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)
Secondary	Maximum Observed blood Concentration (Cmax) of DHES0815A		Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)
Secondary	Minimum Observed blood Concentration (Cmin) of DHES0815A		Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)
Secondary	Clearance of DHES0815A		Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)
Secondary	Volume of Distribution at Steady State (Vss) of DHES0815A		Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)
Secondary	Percentage of Participants with Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)		From start of treatment until confirmation of complete response (CR) or partial response (PR) (up to approximately 45 months)
Secondary	Duration of Response (DoR) Assessed According to RECIST v1.1		From the initial CR or PR to the time of disease progression (PD) or death, whichever occurs first (up to approximately 45 months)
Secondary	Percentage of Participants with Anti-Drug Antibody (ADA) to DHES0815A		Pre-dose (0 hours) on Day 1 up to 42 days after last infusion (up to approximately 45 months)