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

Genentech

Status and phase: Completed; Phase 1

Conditions: Breast Cancer

Treatments: Drug: DHES0815A

Study type: Interventional

Funder types: Industry

Identifiers

NCT03451162

GO39869

Details and patient eligibility

About

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.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 (CNS) metastases
• Cardiopulmonary dysfunction, including inadequate left ventricular ejection function at baseline, less than 50% by either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• QT interval corrected through use of Fridericia's formula (QTcF) > 470 milliseconds (ms)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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14 participants in 2 patient groups

Dose Escalation Cohort: DHES0815A

Experimental group

Description:

Participants will receive DHES0815A in escalating doses in the dose-escalation cohort of the study. Participants will receive additional infusions of DHES0815A on Day 1 of subsequent cycles provided that they meet the protocol specified criteria for acceptable toxicity and ongoing clinical benefit.

Treatment:

Drug: DHES0815A

Dose Expansion Cohort: DHES0815A

Experimental group

Description:

Participants will be treated at or below the Maximum Tolerated Dose (MTD) of DHES0815A (based on the review of the totality of the data) to obtain additional safety, tolerability, PK, and anti-tumor activity data.

Treatment:

Drug: DHES0815A