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.
Authors: Takahiro Kogawa, Toshinari Yamashita, Takanori Ishida, Kan Yonemori, Hiroji Iwata, Akihiko Shimomura, Kenjiro Aogi, Kenichi Inoue, Toru Mukohara, Takahiro Nakayama, Hitomi Sakai, Shigehisa Kitano, Shingo Kobayashi, Takuya Nakada, Ippei Suzuki, Yohei Otake, Junji Tsurutani
Journal: Journal of Clinical Oncology (2024)

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]