Phase 2 Trial Tests Culmerciclib Plus Endocrine Therapy in Advanced Breast Cancer

First-line treatment with the CDK2/4/6 inhibitor culmerciclib in combination with an aromatase inhibitor achieved a confirmed objective response rate of 64.1% (29/39; 95% CI 47.18, 78.80) per RECIST v1.1 among patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer, according to results from a single-arm phase 2 trial published in Breast Cancer Research.

The clinical trial enrolled 39 women with HR+/HER2- advanced breast cancer who had received no prior systemic treatments in the metastatic setting. Participants received oral culmerciclib at a dose of 180 mg per day alongside an oral aromatase inhibitor selected at the investigator’s discretion, consisting of either letrozole at 2.5 mg per day (n = 21) or anastrozole at 1 mg per day (n = 18). The primary endpoint of the trial was confirmed objective response rate per RECIST v1.1, while secondary endpoints included progression-free survival, overall survival, duration of response, clinical benefit rate, disease control rate, and treatment safety.

Across the full analysis set of 39 patients, the disease control rate reached 89.7% (35/39; 95% CI 75.78, 97.13) and the clinical benefit rate was 82.1% (32/39; 95% CI 66.47, 92.46), with a median duration of response of 34.1 months (95% CI 16.36, not reached [NE]). Over a median follow-up period of 28.9 months, the median progression-free survival was 24.9 months (95% CI 13.83, NE), and the 24-month overall survival rate was 82.6% (95% CI 65.26, 91.78). Subgroup analyses indicated numerically higher antitumor responses in patients without visceral metastasis, who exhibited an objective response rate of 88.9% (95% CI 65.29, 98.62) and a median progression-free survival that was not reached (95% CI 19.25, NE), as well as in premenopausal or perimenopausal patients, who demonstrated an objective response rate of 80.0% (95% CI 51.91, 95.67) and a median progression-free survival of 35.9 months (95% CI 24.94, NE).

Regarding safety, the most common grade 3 or higher treatment-related adverse events observed were hypertriglyceridemia in 20.5% of patients and decreased white blood cell count in 15.4%. The investigators concluded that culmerciclib combined with an aromatase inhibitor demonstrated promising antitumor activity and a tolerable safety profile as a first-line regimen in this patient population, while noting that further validation of the findings is needed. The trial was registered on May 12, 2026, at the Chinese Clinical Trial Registry under registration number ChiCTR2600124423.

Subject of Research: First-line culmerciclib plus endocrine therapy for HR+/HER2- advanced breast cancer

Article Title: Culmerciclib plus endocrine therapy as first-line treatment in patients with HR+/HER2- advanced breast cancer: a single-arm, phase 2 trial

Article References: Gao, Z., Duan, Y., Jiang, C., Jiang, L., Li, X., Dong, F., Jia, Y., Cao, H., E, Y., Jiang, Y., Li, H., & Sun, T. (2026). Culmerciclib plus endocrine therapy as first-line treatment in patients with HR+/HER2- advanced breast cancer: a single-arm, phase 2 trial. Breast Cancer Research. https://doi.org/10.1186/s13058-026-02416-3

Image Credits: AI Generated

DOI: 10.1186/s13058-026-02416-3

Keywords: culmerciclib, endocrine therapy, breast cancer, CDK2/4/6 inhibitor, aromatase inhibitor, phase 2 trial, letrozole, anastrozole, plus, endocrine, therapy, first-line