Clinical efficacy of a novel oral SERD TFX06 in prior fulvestrant-treated ER+/HER2− advanced breast cancer patients in a dose expansion study.

1062 Background: Patients with ER+/HER2- advanced breast cancer who have progressed on prior endocrine therapies, including fulvestrant, represent an area of unmet medical need, particularly those harboring ESR1 mutations. As far as we know, there was limited reports on efficacy of oral SERD in prior fulvestrant treatment progressed patients. TFX06 is an investigational next-generation oral SERD. Here, we report results from a Phase I/Ⅱ study of TFX06 in patients with ER+/HER2- advanced breast cancer who had progressed from prior fulvestrant treatment (NCT05927779). Methods: Eligible patients regardless of their menopausal status, who had received ≥1 lines of endocrine therapy (ET), prior fulvestrant (fulv) treated with or without CDK4/6i, and ≤2 line of chemotherapy in metastatic disease, were allowed to enroll. TFX06 tablets were orally administered at 150mg once daily (QD) in 28-day cycles until disease progression or intolerable toxicity. This analysis focuses on the subgroup with prior fulvestrant exposure. As of cut-off date December 22, 2025, 42 patients received TFX06 monotherapy at 150mg. Median age was 60.5 years (range, 34-73), 76.2% had an ECOG performance status of 1. 88.1% had visceral metastasis, and 16.7% had brain metastasis. The median number of prior endocrine therapies in the advanced or metastatic setting was 2 (range, 1-3), including fulvestrant (100%), CDK4/6i (85.7%) with combination (76.2%). Tumor assessments by investigators according to RECIST v1.1 were performed every eight weeks. Results: Of the 42 enrolled patients, 40 were evaluable for efficacy. In the full analysis set (n=40), median progression-free survival (PFS) was 5.5 months (95% CI, 3.2–7.8). The objective response rate (ORR) was 7.5% (3/40), disease control rate (DCR) was 60.0% (24/40), and clinical benefit rate (CBR) was 44.1% (15/34). In the ESR1-mutant subgroup (n=23), median PFS was 5.7 months (95% CI, 2.5–8.8), ORR was 8.7% (2/23), DCR was 65.2% (15/23), and CBR was 47.1% (8/17). Treatment emergent adverse events (TEAEs) occurred in 95.2% of patients (40/42), with grade ≥3 events in 26.2% (11/42). Most common TEAEs (≥20%) are laboratory abnormalities; they included hypertriglyceridemia (47.6%), increased AST (31.0%), anemia (31.0%), decreased lymphocyte count (23.8%), and decreased white blood cell count (21.4%). No TEAEs led to treatment termination. Conclusions: TFX06 showed promising clinical activity and a manageable safety profile in patients who progressed from prior fulvestrant-treatments including combination with CDK4/6i in ER+/HER2- advanced breast cancer, including those with ESR1 mutations. These findings support further development of TFX06 as a potential therapeutic option in this population. Clinical trial information: NCT05927779 .