Clinical trial · Interventional
Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer
A Phase 1-2 Multicenter, Open Label Trial of H3B-6545, a Covalent Antagonist of Estrogen Receptor Alpha, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The primary purpose of phase 1 portion of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of H3B-6545 in women with locally advanced or metastatic estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer. The primary purpose of phase 2 portion of this study is to estimate the efficacy of H3B-6545 in terms of best overall response rate, duration of response (DoR), clinical benefit rate (CBR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in all participants with ER-positive, HER2-negative breast cancer and in those with and without ER alpha mutation (including a clonal estrogen receptor 1 gene \[ESR1\] Y537S mutation).
Conditions
Conditions (8)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Adenocarcinoma | Breast Adenocarcinoma | ONTOLOGY_EXACT | 0.98 |
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
| Breast Cancer Female | — | UNRESOLVED | — |
| Breast Neoplasms | Breast Neoplasm | ONTOLOGY_EXACT | 0.98 |
| Cancer, Breast | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
| ER Positive | — | UNRESOLVED | — |
| Estrogen-receptor Positive Breast Cancer | — | UNRESOLVED | — |
| Estrogen Receptor Positive Tumor | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| H3B-6545 | Drug | Selective Estrogen Receptor Covalent Antagonist H3B-6545 | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- H3B-6545 Arm 1: Dose escalation
- interventionNames
- Drug: H3B-6545
- type
- EXPERIMENTAL
- label
- H3B-6545 Arm 2: Phase 2
- interventionNames
- Drug: H3B-6545
Primary outcomes (7)
- measure
- Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
- timeFrame
- Cycle 1 (Cycle length=28 days)
- description
- DLT was graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. DLTs were defined as the following events that occurred in Cycle 1, for which a causal relationship with the study drug could not be ruled out: febrile neutropenia; Grade 4 neutropenia that was not resolved within 7 days; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia lasting greater than (\>) 7 days or associated with clinically significant bleeding; Grade 4 vomiting and diarrhea; Grade 3 vomiting and diarrhea lasting \>72 hours despite treatment; Grade 4 electrolyte abnormality or Grade 3 abnormality lasting \>24 hours; Grade 3 or 4 serum creatinine or bilirubin increase; Grade 4 biochemistry or Grade 3 lasting \>7 days; Grade 4 or Grade 3 or intolerable Grade 2 toxicities of any non-hematologic adverse event.
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: 1. Pre- or post-menopausal women. 2. ER-positive, HER2-negative breast cancer that is advanced or metastatic. 3. Progressed on prior therapy. Multiple prior lines of therapy allowed in Phase 1 and 2. Participants under amendment 6 (or subsequent amendments) must have received prior cyclin-dependent kinase (CDK4/6) inhibitor therapy. Up to one prior chemotherapy in the metastatic setting is allowed. 4. A recent archival tumor tissue obtained within 6 months prior to enrollment or a fresh tumor biopsy must be provided. A second biopsy after initiating trial therapy is not required. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 6. Adequate bone marrow and organ function. 7. Participants under amendment 6 (or subsequent amendments) must have measurable disease at baseline as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. 8. Participants under amendment 6 (or subsequent amendments) must have ESR1 Y537S mutation in absence of ESR1 D538G mutation as per the results of a central laboratory from a Nucleic Acids Whole Blood sample. Exclusion Criteria: 1. Participants must have at least one measurable lesion. 2. Participant with inflammatory breast cancer. 3. Participant has received more than one prior chemotherapy regimen for metastatic disease (Phase 2 only). 4. Females of childbearing potential who are unable or unwilling to follow adequate contraceptive measures.
References
Publications (2)
- DERIVEDHamilton E, Pluard T, Wang JS, Morikawa A, Johnston S, Dees EC, Vaklavas C, Armstrong A, Munster P, Unni N, Wright GS, Kayali F, Song T, Rong Y, Yamaguchi K, Juric D. Phase 1/2 study of H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive, HER2-negative breast cancer. Breast Cancer Res. 2025 Aug 19;27(1):151. doi: 10.1186/s13058-025-02069-8. PMID 40830892
- DERIVEDFurman C, Puyang X, Zhang Z, Wu ZJ, Banka D, Aithal KB, Albacker LA, Hao MH, Irwin S, Kim A, Montesion M, Moriarty AD, Murugesan K, Nguyen TV, Rimkunas V, Sahmoud T, Wick MJ, Yao S, Zhang X, Zeng H, Vaillancourt FH, Bolduc DM, Larsen N, Zheng GZ, Prajapati S, Zhu P, Korpal M. Covalent ERalpha Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer. Mol Cancer Ther. 2022 Jun 1;21(6):890-902. doi: 10.1158/1535-7163.MCT-21-0378. PMID 35642432