Camizestrant in combination with three globally approved CDK4/6 inhibitors in women with ER+, HER2- advanced breast cancer: Results from SERENA-1.

PURPOSE This trial investigated safety and tolerability of camizestrant with CDK4/6 inhibitors (CDK4/6i), in women with ER+, HER2- advanced breast cancer. PATIENTS AND METHODS SERENA-1 (NCT03616587) is a Phase 1, multi-part, open-label study in women with refractory ER+, HER2- advanced breast cancer. Patients received oral once-daily camizestrant 75 or 150 mg plus abemaciclib; camizestrant 75, 150, or 300 mg plus palbociclib; or camizestrant 75 mg plus ribociclib 400 or 600 mg. Safety/ tolerability, pharmacokinetics, efficacy, and impact on ESR1m ctDNA was assessed. RESULTS By September 16, 2024 (data cut-off), 53 patients had received camizestrant plus abemaciclib, 78 plus palbociclib, and 60 plus ribociclib. Patients had a median of 2 (range 0-7) prior regimens for advanced disease; 83% had received a prior CDK4/6i and 59% prior fulvestrant. The most common TEAE for camizestrant 75 mg (Phase 3 dose) plus each CDK4/6i were diarrhoea (with abemaciclib [87.5%]), and neutropenia (with palbociclib [80%] and ribociclib [32.1% for 400 mg, 53.1% for 600 mg]). Median camizestrant tmax was ~4 hours post dose across combinations, with an estimated half-life of 9.5-17 hours. No clinically meaningful drug-drug interactions. were evident. In this heavily pre-treated population, CBR24 was 49.5% and median PFS was 7.4 months (95% CI: 5.3-9.3), with anti-tumor activity across all combinations, including patients previously treated with CDK4/6i and/or fulvestrant, with or without ESR1m. CONCLUSION Camizestrant is well-tolerated, with anti-tumor activity in combination with CDK46i. These results support evaluation of camizestrant 75 mg plus standard CDK4/6i doses in Phase 3 trials.