Clinical Summary:

• Design/Population: The BTX-9341-101 study evaluated BTX-9341 alone or in combination with fulvestrant in heavily pretreated patients with HR-positive, HER2-negative advanced breast cancer. 
• Key Outcomes:  BTX-9341 demonstrated manageable toxicity, sustained target engagement, and preliminary clinical activity across dose cohorts, including in patients with prior CDK4/6 inhibitor exposure.
• Clinical Relevance: These results support further development of BTX-9341 as a next-generation strategy. 

Results from the phase 1 BTX-9341-101 trial demonstrated that BTX-9341, a first-in-class CDK4/6 degrader, shows encouraging efficacy and safety among patients with HR-positive, HER2-negative advanced or metastatic breast cancer who experience disease progression after CDK4/6 inhibition. 

These results were presented by Matthew Goetz, MD, Mayo Clinic, Rochester, Minnesota, at the 2026 European Society for Medical Oncology (ESMO) Breast Cancer Congress in Berlin, Germany.

In this open-label study, 28 patients who received ≤6 lines of prior treatment in the advanced or metastatic setting received 50 to 100 mg of once daily BTX-9341 either alone or in combination with 25 to 75 mg of fulvestrant. Dose escalation was achieved using accelerated titration and Bayesian Optimal Interval designs. Primary end points included safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy.

At analysis, no dose-limiting toxicities or serious adverse events were reported. The most frequently reported adverse events included neutrophil count decrease, lymphocyte count decrease, and white blood cell count decrease, all of which were low grade. Grade 3/4 events were manageable, and no treatment-related discontinuations were reported. 

Across all evaluable patients, the longest treatment duration was 15 cycles. The clinical benefit rate was 53.3% in patients who were treated for at least 6 months (n = 15) and 70% in patients who received 1 priorCDK4/6 inhibitor (n = 10), regardless of resistance-associated genomic alterations.

Pharmacokinetic analyses demonstrated approximately 2-fold accumulation consistent with a 24-hour half-life. Biomarker analyses showed >50% reductions in serum thymidine kinase activity in most evaluable patients, along with evidence of durable ctDNA and protein suppression consistent with on-target CDK4/6 inhibition. 

These findings support “continued development in [HR-positive, HER2-negative advanced or metastatic breast cancer] following prior CDK4/6i therapy,” concluded Dr Goetz. 

Source:

Goetz MP. Patnaik A, Block MB, et al. Dose optimization of BTX-9341, a first-in-class CDK4/6 bifunctional degrader, in CDK4/6 inhibitor-pretreated HR+/HER2- advanced/metastatic breast cancer. Presented at European Society for Medical Oncology (ESMO) Breast Cancer Congress; March 6 - 8, 2026; Berlin, Germany. 421RO.