Samuraciclib + fulvestrant shows higher clinical benefit and numerically longer PFS after CDK4/6 inhibition in randomized Phase 2 breast cancer trial

Samuraciclib (CT7001) is an oral, selective CDK7 inhibitor designed to disrupt estrogen receptor-driven transcriptional programs that can sustain tumor growth after resistance to CDK4/6 inhibitors. In the three-arm, randomized Phase 2 SUMIT-BC trial (NCT05963984), 59 patients with advanced HR+/HER2− breast cancer previously treated with CDK4/6 inhibitors received samuraciclib 360 mg + fulvestrant (n=20), samuraciclib 240 mg + fulvestrant (n=19), or fulvestrant alone (n=20). The primary endpoint, 24-week clinical benefit rate (CBR), was 60.0% and 63.2% with the combinations versus 40.0% with fulvestrant alone. Median progression-free survival (PFS) was numerically longer at 7.8 and 8.5 months versus 5.6 months, although the small trial was not powered to establish a definitive PFS advantage. Objective response rates were 33.3%, 21.4%, and 14.3%, respectively. Gastrointestinal toxicity was common, with grade 3 diarrhea in 10.0% and 5.3% of the combination groups and grade 3 nausea in 15.0% at 360 mg. Dose reductions were required in 50.0% and 31.6% of patients, respectively. Exploratory subgroup analyses suggested greater benefit in patients without detectable TP53 mutations, without baseline liver metastases, or with at least 12 months of prior CDK4/6 inhibitor treatment. These findings suggest activity beyond fulvestrant alone, but the small sample and differences between treatment groups limit interpretation, particularly when compared with contemporary biomarker-selected endocrine and targeted therapies.