Abstract RF01-04: Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification

Abstract Background: Fibroblast growth factor receptor 1 (FGFR1) gene amplification and overexpression is associated with an adverse prognosis in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) breast cancer and is observed in ~10% of all invasive breast cancers. The phase 2 FOENIX-MBC2 study (NCT04024436) was designed to evaluate the effect of futibatinib, a highly selective and potent irreversible covalent inhibitor of FGFR1–4 (FDA-approved for intrahepatic cholangiocarcinoma), used either alone or in combination with fulvestrant in patients with metastatic breast cancer. Here, we report final efficacy and safety data for the cohort of patients receiving futibatinib plus fulvestrant for HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification. Methods: Patients were eligible if they had disease progression after prior therapy for advanced/metastatic disease, had measurable disease per RECIST v1.1, had an ECOG performance status of 0 or 1, were fulvestrant-naïve, and had previously received 1–2 endocrine-containing therapies, ≤1 chemotherapy regimen, and a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor for advanced cancer (unless ineligible). High-level FGFR1 gene amplification, determined in tumor tissue using next-generation sequencing, fluorescence in situ hybridization (FISH), or similar assays, was defined as FGFR1/centromere 8 ratio ≥5 or FGFR1 copy number ≥10 signals per cell. Local FGFR1 determination results were confirmed in tumor tissue by a central laboratory using FISH. Patients received oral futibatinib 20 mg once daily and standard fulvestrant dosing until disease progression, unacceptable toxicity, or other discontinuation criteria were met. The primary endpoint was the 6-month progression-free survival (PFS) rate. Key secondary endpoints included objective response rate (ORR), PFS, and overall safety. Results: Overall, 22 female patients were enrolled in this cohort. Patients were a median age of 58 years, had received a median of 3 lines of any prior systemic anticancer therapy, and had all received CDK4/6 inhibitor pretreatment. PFS at 6 months was observed in 10 (45.5%) patients (95% CI: 24.4, 67.8) and the median PFS was 7.2 (95% confidence interval [CI]: 2.1, 7.6) months. Four patients had a confirmed partial response (ORR: 18.2%; 95% CI: 5.2, 40.3). The median duration of response was 6.3 (range: 3.3–12.8) months. All patients had ≥1 treatment-related adverse event (TRAE), the most common being hyperphosphatemia (95.5%), alopecia (54.5%), constipation (45.5%), and dry mouth (40.9%). There were 5 (22.7%) patients with a Grade 3 TRAE (no Grade 4 or 5). TRAEs leading to study treatment interruption or reduction were seen in 9 (40.9%) and 15 (68.2%) patients, respectively. There were 2 (9.1%) patients who had TRAEs leading to study treatment discontinuation. No treatment-related serious adverse events were reported. Conclusions: Futibatinib plus fulvestrant showed antitumor activity in patients with advanced HR+/HER2− breast cancer with FGFR1 amplification progressing on prior CDK4/6 inhibitors, with a numerically higher ORR and doubling in PFS relative to historical fulvestrant results in post-CDK4/6 patients. The safety profile was consistent with those of the individual study drugs. Further biomarker work is ongoing. Citation Format: Senthil Damodaran, Fabrice André, Nisha Unni, Marta Ferreira, Karthik Giridhar, Brooke Daniel, Marco Colleoni, Luis Costa, Thomas Bachelot, Ciara O’Brien, Gail Wright, Masashi Shimura, Gareth Tomlinson, Maciej Gil, Nicholas Turner. Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF01-04.