Phase Ib trial of tasurgratinib (E7090) with or without endocrine therapies for patients (pts) with ER+, HER2− recurrent/metastatic breast cancer (BC) after receiving a CDK4/6 inhibitor.

3103 Background: Previous preclinical study has shown the antitumor activity of E7090, a novel selective FGFR1–3 inhibitor (i), with endocrine therapy (ET) for ER+, HER2− BC with FGFR signaling dependency after CDK4/6i exposure. In Study 102, we evaluated E7090 with/without ET in pts with ER+, HER2− recurrent/metastatic BC following a CDK4/6i. Methods: Primary objectives were to evaluate the tolerability/safety of each cohort and determine a recommended dose (RD) for future study. Secondary objectives included evaluating ORR, disease control rate (DCR; complete response CR + partial response PR + stable disease SD), clinical benefit rate (CBR; CR + PR + SD for ≥23 wks), PFS, and OS. All pts had ER+, HER2− recurrent/metastatic BC and had received a CDK4/6i. In part 1, pts were treated with fulvestrant (FUL) 500 mg + E7090 (105 mg Cohort 1 or 140 mg Cohort 2), or exemestane 25 mg + E7090 (105 mg Cohort 3 or 140 mg Cohort 4). In part 2, pts with high FGFR1/2 protein expression by IHC were treated with E7090 140 mg monotherapy (Cohort 5). In part 3, pts were treated with the RD (Cohort 6) to evaluate preliminary efficacy and safety; these pts were not selected based on their level of FGFR expression. Pts were dosed in 28-day cycles (C). Results: 19 Pts were enrolled and treated in parts 1–2 (Cohort 1: n=3; Cohort 2: n=3, Cohort 3: n=3; Cohort 4: n=9); only 1 pt was enrolled to Cohort 5 as a correlation between efficacy and expression of FGFR1/2 protein was not seen in part 1. 2 Pts in Cohort 4 had dose-limiting toxicities during C1 (grade 2 serous retinal detachment and grade 3 hypertension/grade 2 hyperphosphatemia). A higher % of pts receiving E7090 140 mg had dose reduction (58.3% vs 16.7%) than E7090 105 mg. E7090 105 mg + FUL 500 mg was considered the RD. Of the 4 responders in part 1, 3 pts received E7090 for more than 2 years. As of the data cutoff date (August 21, 2023), 32 pts were treated with E7090 105 mg + FUL 500 mg in part 3; 10 pts (31.3%) received 2 lines of prior anticancer therapy for metastatic/locally advanced disease. The ORR was 21.9% (95% CI 9.3–40.0; Table). Median (m) PFS was 5.4 mos (95% CI 3.5–not estimable NE). All pts had a treatment-related adverse event (TRAE), most commonly hyperphosphatemia (n=32). 9 Pts (28.1%) had a grade ≥3 TRAE, most commonly neutrophil count decreased (n=3). No pts withdrew from treatment due to TRAEs. Conclusions: E7090 + FUL had a manageable safety profile. The combination showed promising preliminary antitumor activity in ER+ HER2− BC previously treated with a CDK4/6i; its ORR was 21.9%. Our results support the further development of this combination for HR+/HER2− advanced BC after a CDK4/6i. Clinical trial information: NCT04572295 . Table: see text