Phase I study of H3B-6545 in patients with estrogen receptor-positive breast cancer
Abstract
Background: This phase I study (NCT04568902) evaluated a novel selective estrogen receptor (ER)-α covalent antagonist (H3B-6545) at doses of 300-450 mg in Japanese women with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced/metastatic breast cancer (mBC).
Patients and methods: This study consisted of three parts. In the dose-escalation (DE) part, two dose levels [300 and 450 mg once daily (QD)] were evaluated. The next two parts (antihistamine prophylactic administration and randomization) evaluated oral antihistamines for rash occurrence. Primary endpoints were dose-limiting toxicities (DLTs) and safety; secondary endpoints included objective response rate [ORR; i.e. complete response (CR) + partial response (PR)] and clinical benefit rate [CBR; i.e. CR + PR + stable disease (SD) for ≥23 weeks].
Results: Thirty-three patients were enrolled to receive H3B-6545 (300 mg, n = 3; 450 mg with antihistamine, n = 15; 450 mg without antihistamine, n = 15). Median age was 57 years. The median number of prior therapies for mBC was three including fulvestrant (78.8%) and cyclin-dependent kinase 4/6 inhibitors (72.7%). In the DE part, no DLTs were observed with H3B-6545 300 mg. One DLT (grade 3 QT interval prolonged) occurred among six patients with H3B-6545 450 mg. Overall, the most common adverse event (AE) was sinus bradycardia (93.9%); the most common grade 3 AE was anemia (15.2%). No grade 4/5 AEs were reported. Rash maculopapular or rash occurred in…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 15 participants or records.
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