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Abstract Background: Triple-negative breast cancer (TNBC) accounts for ~15% of breast cancers and represents an aggressive subtype with limited targeted therapeutic options. Fibroblast growth factor receptor (FGFR) signaling plays an important role in breast tumorigenesis and metastasis. The phase 2 FOENIX-MBC2 study (NCT04024436) was designed to evaluate responses to futibatinib, a highly selective and potent irreversible covalent inhibitor of FGFR1–4 (FDA-approved for intrahepatic cholangiocarcinoma), in patients with metastatic breast cancer. Here, we report final efficacy and safety data for futibatinib in the cohort of patients with advanced/metastatic TNBC harboring FGFR2 gene amplification. Methods: Eligible patients had locally advanced/metastatic TNBC with measurable disease per RECIST v1.1, an ECOG performance status of 0/1, and progressive disease after ≥1 prior chemotherapy-containing regimen for advanced disease. Patients were positive for FGFR2 gene amplification determined by analysis of tumor tissue or circulating tumor DNA. Patients received oral futibatinib 20 mg once daily until disease progression, unacceptable toxicity, or other discontinuation criteria were met. The primary endpoint was objective response rate (ORR) by RECIST v1.1 in patients with centrally confirmed FGFR2 amplification. Responses (complete response and partial response) required confirmation after at least 4 weeks. Secondary endpoints included the 6-month progression-free survival (PFS) rate, PFS, duration of response (DOR), and overall safety. Results: Overall, 21 female patients with TNBC were enrolled (median age: 53 years) in this cohort. Patients had received a median 5 lines of prior systemic therapy. Overall, 2 patients had a confirmed partial response (ORR: 9.5%; 95% confidence interval CI: 1.2, 30.4), with a median DOR of 6.1 months (range: 3.1−9.2 months). Five (23.8%) patients had stable disease. PFS at 6 months was observed in 4 patients (19.0%; 95% CI: 5.4, 41.9) and the median PFS was 1.9 months (95% CI: 1.6, 4.0). Twenty patients (95.2%) had ≥1 treatment-related adverse event (TRAE), including 7 (33.3%) with a Grade 3 TRAE (no Grade 4 or 5). Common TRAEs (any grade) included hyperphosphatemia (85.7% of patients), constipation, diarrhea, fatigue, and dry skin (each in 23.8% of patients). Anemia was the only Grade 3 TRAE observed in more than 1 patient (n=2, 9.5%). Overall, 28.6% of patients had a serious adverse event (SAE; any cause), and 1 patient had an SAE leading to death (ischemic stroke). None of the SAEs or deaths were considered treatment-related. Conclusions: In heavily pretreated patients with metastatic TNBC harboring FGFR2 gene amplification, futibatinib monotherapy demonstrated modest anticancer activity. Futibatinib was tolerable and had an acceptable safety profile, consistent with previous data. Further biomarker work to identify patients who might benefit most from futibatinib is ongoing. Clinical trial information: NCT04024436 Citation Format: Antonio Giordano, Nisha Unni, Senthil Damodaran, Hope Rugo, Timothy Crook, Thomas Bachelot, Federico Piacentini, Hector Soto Parra, Ian Krop, Masashi Shimura, Gareth Tomlinson, Maciej Gil, Nicholas Turner, Fabrice André. Efficacy and safety of futibatinib in patients with locally advanced/metastatic triple-negative breast cancer harboring FGFR2 gene amplification: final results from the phase 2, open-label FOENIX-MBC2 study 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 PO4-06-07.
Giordano et al. (Thu,) studied this question.