Abstract PS4-06-06: Tfx06 dose expansion study showed favorable safety and efficacy in patients with er+ /her2- breast cancer in a phase 2 study

Background: TFX06, a third-generation oral CERAN/SERD, was evaluated in a multicenter Phase 1a/b study (NCT05927779) in patients with ER+/HER2- locally advanced and/or metastatic breast cancer (Zhang J, et al., 2024 SABCS annual meeting). The recommended dose was established at 150mg QD. Dose expansion study at 150mg had been initiated, and this abstract summarizes our key findings. Patients and Methods: Eligible patients regardless of their menopausal status, who had received ≥1 lines of endocrine therapy (ET), prior treatment with CDK4/6i and fulvestrant (fulv); and ≤2 line of chemotherapy for metastatic disease were allowed to enroll. TFX06 tablets were orally administered 150mg once daily (QD) every 28 days of treatment cycle until disease progression or intolerable toxicity. As of cut-off date June 30, 2025, 57 patients received TFX06 monotherapy at 150mg dose, median age of 60 years (range 34-74) with ECOG score of 0-1. 78.9% of patients enrolled had visceral metastasis in liver, lung or both, and 14% of patients had brain metastasis. Median number of prior endocrine therapies were 2 (1-4) including fulvestrant (56.1%), CDK4/6i (61.4%) and combination of both (38.6%) and a median number of chemotherapies was 1 (0-3). Tumor assessments by investigators according to RECIST v1.1 were performed every eight weeks. Results: TFX06 was well tolerated. The most common (≥20% of patients) treatment-emergent adverse events (TEAEs) were hypertriglyceridemia, AST increased, anemia, lactate dehydrogenase increased and hypoalbuminaemia. The incidence of nausea, diarrhea and vomiting was low (7.0%, 5.3% and 1.8%, respectively). In addition, no ocular toxicity reported. Among 55 evaluable patients, there were 6 partial responses (ORR was 10.9%); clinical benefit rate (CBR) was 45.5% and mPFS for the overall population was 5.5 months. mPFS for ESR1m detectable and ESR1m-undetectable patients were 5.7 months and 4.6 months respectively. In addition, among the 13 patients who had prior CDK4/6i treatment and with detectable ESR1 mutation, the CBR was 46.2% and mPFS was 5.6 months. Among 21 patients who had prior fulvestrant+CDK4/6i combo treatment, CBR was 42.9% and mPFS was 3.7 months, while ESR1 detectable mutation patients, CBR was 55.6% and mPFS was 5.6 months. Notably, of four patients with measurable brain lesions, three were evaluable: two showed >70% brain lesion reduction (PR), one had stable disease, suggesting TFX06 had intracranial activity. Conclusions: TFX06 at 150 mg QD dose expansion trial enrolled endocrine therapy heavily treated patients, including prior treatment with combination of fulvestrant and CDK4/6 inhibitor progressed patients. TFX06 demonstrated favorable safety and clinical efficacy even in this hard-to-treat patient population. Citation Format: Y. Chen, J. Zhang, H. Guo, Y. Sun, Y. Wang, Z. Zhang, T. Yao, Y. Shi, H. Zhang, Y. Chen, Y. Lu, J. Song, P. Li, D. Fang, W. Sha, C. Z. Ding. Tfx06 dose expansion study showed favorable safety and efficacy in patients with er+ /her2- breast cancer in a phase 2 study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-06-06.