Evidence map›Paper›PMID 40830892›Full record

Trial reportBreast cancer research : BCR2025

Phase 1/2 study of H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive, HER2-negative breast cancer.

Erika Hamilton, Timothy Pluard, Judy S Wang, Aki Morikawa, Stephen Johnston, E Claire Dees, Christos Vaklavas, Anne Armstrong, Pamela Munster, Nisha Unni and 6 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter StudyClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03250676 (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), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03250676 phase1 / phase2completednot on this map

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

TypeinterventionalSponsorEisai Inc.Ran2017 to 2023Enrolled151ConditionsBreast Neoplasms, Breast Cancer, Estrogen-receptor Positive Breast Cancer, Cancer, BreastArmsH3B-6545
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Erika HamiltonBreast Cancer Research Program, Sarah Cannon Research Institute, Nashville, TN, USA. erika.hamilton@scri.com.
Timothy PluardKoontz Center for Advanced Breast Cancer, Saint Luke's Cancer Institute, Kansas City, MO, USA.
Judy S WangHematology and Oncology, Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, USA.
Aki MorikawaDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Stephen JohnstonBreast Unit, Royal Marsden NHS Foundation Trust, London, UK.
E Claire DeesDepartment of Medicine, Division of Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Christos VaklavasDepartment of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Anne ArmstrongDivision of Cancer Studies, University of Manchester, Manchester, UK.
Pamela MunsterDivision of Hematology and Oncology, University of California, San Francisco, CA, USA.
Nisha UnniDepartment of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Gail S WrightMedical Oncology, Florida Cancer Specialists & Research Institute/Sarah Cannon Research Institute, Trinity, FL, USA.
Fadi KayaliHematology and Oncology, Florida Cancer Specialists, Lakewood Ranch/Sarasota, FL, USA.
Tingting SongEisai Inc, Nutley, NJ, USA.
Yuanxin RongEisai Inc, Nutley, NJ, USA.
Kohei YamaguchiEisai Co., Ltd, Tokyo, Japan.
Dejan JuricMassachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough endocrine therapies, alone or in combination with CDK4/6 inhibitors, have led to notable improvements in the treatment of estrogen receptor-positive (ER+) breast cancer, progression is inevitable for most patients. We report dose escalation and expansion data from a trial of H3B-6545 (a novel selective ER covalent antagonist that inactivates wild-type and mutant ERα) in women with locally advanced/metastatic ER+, HER2-negative breast cancer (BC).

methodsThis study was a multicenter, open-label, phase 1/2 trial. Women ≥ 18 years of age with ER+, HER2 − BC whose disease progressed on their most recent therapy were eligible. Prior therapy must have included at least 2 hormonal therapies (HTs), or 1 HT and 1 chemotherapy, or 1 HT and a CDK4/6 inhibitor. In phase 1, H3B-6545 was administered orally once daily at doses of 100–600 mg. In phase 2, the efficacy of the recommended phase 2 dose (RP2D) determined in phase 1 was examined in additional patients, including those with/without ERα mutation. The primary endpoints were RP2D determination (phase 1) and objective response rate (ORR) (phase 2, investigator-assessed per RECIST v1.1). Additional primary endpoints (phase 2) included progression-free survival (PFS) and overall survival (OS), per Kaplan-Meier estimates.

results151 Patients were treated across phases. During phase 1, 2 DLTs (drug eruption and fatigue, both grade 3) were observed at the 600 mg dose, and 450 mg was deemed the RP2D. In the total population (phases 1 and 2), all patients experienced ≥ 1 treatment-emergent adverse event (TEAE), and 50.3% had grade 3–4 TEAEs, with no grade 5 TEAEs observed. In phase 1, the overall ORR was 7.5% (95% CI 1.6–20.4). The ORR in all response-evaluable patients treated at 450 mg (n = 94) was 20.2% (95% CI 12.6–29.8). Patients with clonal ESR1 Y537S mutation had an ORR of 32.1% (95% CI 15.9–52.4). For all patients who received H3B-6545 450 mg, median PFS was 4.6 months (95% CI 3.5–6.7) and median OS was 21.5 months (95% CI 16.6–25.5).

conclusionsResults suggest that H3B-6545 may be further investigated as an endocrine therapy option for patients with previously treated metastatic ER + BC.

trial registrationNCT03250676. Registered August 11, 2017.

Indexed as

Breast NeoplasmsReceptors, EstrogenAdultAgedErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaFemaleHumansMiddle AgedERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaReceptors, EstrogenBreast cancerEndocrine therapyEstrogen receptor-positiveH3B-6545HER2-negative

Identifiers

PMID40830892
PMCPMC12363031

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.