Phase 1
Completed N=14
Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer
Source: ClinicalTrials.gov NCT03451162 ↗Enrolled (actual)
14
Serious AEs
28.6%
Results posted
Aug 2024
Primary outcomePrimary: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 — 3; 3; 3; 3 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 |
3; 3; 3; 3; 2; 1 | — |
| PRIMARY Number of Participants With Dose-limiting Toxicity (DLT) |
0; 0; 0; 0; 0 | — |
| PRIMARY Duration of Treatment |
64.0; 208.0; 43.0; 64.0; 43.0 | — |
| PRIMARY Total Cumulative Dose |
882.33; 2143.00; 342.27; 1340.20; 548.80 | — |
| PRIMARY Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan |
59.00; 63.33; 64.00; 59.67; 62.50; 0.33 | — |
| SECONDARY Concentration of DHES0815A Total Antibody |
NA; NA; NA; NA; NA; 13100 | — |
| SECONDARY Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA) |
NA; NA; NA; NA; NA; 90.5 | — |
| SECONDARY Concentration of Plasma Unconjugated PDB-MA |
NA; NA; NA; NA; NA; 0.107 | — |
| SECONDARY Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Duration of Response (DoR) Assessed According to RECIST v1.1 |
NA | — |
| SECONDARY Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A |
1; 0; 0; 0; 1; 0 | — |
Eligibility 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)
Data sourced from ClinicalTrials.gov (NCT03451162). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.