Study of Efficacy, Safety, and Pharmacokinetics of FCN-437c in Combination With Fulvestrant or Letrozole+Goserelin

Summary

This is a multicenter, open-label clinical study to evaluate the safety and antitumor activity of FCN-437c in combination with Fulvestrant for the treatment of post-menopausal female patients with ER+ and HER2- advanced breast cancer, FCN-437c in combination with Letrozole + Goserelin for the treatment of pre-menopausal female patients with ER+ and HER2- advanced breast cancer, and to evaluate the PK characteristics of the FCN-437c combination therapies. This study is consist of two cohorts, Cohort 1: FCN-437c in combination with Fulvestrant (1st or 2nd line treatment for postmenopausal ER+, HER2-advanced breast cancer); Cohort 2: FCN-437c in combination with Letrozole + Goserelin (1st line treatment for premenopausal ER+, HER2- advanced breast cancer). Thirty patients will be enrolled in each cohort, for a total of 60 patients. Tumor Assessment: Tumor evaluation will be performed every 8 weeks (±7 days) according to RECIST version 1.1 until disease progression, withdrawal of informed consent, or death; for patients who discontinue the drug due to toxicity, imaging evaluation is required until disease progression. End of Treatment and End of Study: End of Study (EOS) is defined as 2 years after the last patient's first dose or the end of treatment (whichever is earlier). At the end of the study, the investigator will decide whether the patients whose disease has not progressed shall continue taking FCN-437c and other combination agents or not based on clinical benefit. Cohort 1: Post-menopausal patients diagnosed with ER+, HER2- advanced breast cancer, who have not received prior systemic therapy for advanced breast cancer, or who have disease progression determined by imaging assessment during their 1st line endocrine therapy; Cohort 2: Pre-menopausal patients diagnosed with ER+, HER2- advanced breast cancer, who have not received prior systemic therapy for advanced breast cancer;

Timeline

Start

2020-06-30

Primary completion

2021-12-30

Completion

2023-06-30

Publications

• Background Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Vidam G, Wang Y, Rodriguez Lorenc K, Miller M, Taran T, Jerusalem G. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol. 2018 Aug 20;36(24):2465-2472. doi: 10.1200/JCO.2018.78.9909. Epub 2018 Jun 3.
• Background Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva-Vazquez R, Jung KH, Chakravartty A, Hughes G, Gounaris I, Rodriguez-Lorenc K, Taran T, Hurvitz S, Tripathy D. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019 Jul 25;381(4):307-316. doi: 10.1056/NEJMoa1903765. Epub 2019 Jun 4.
• Background Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. doi: 10.1200/JCO.2017.73.7585. Epub 2017 Jun 3.
• Background Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-439. doi: 10.1016/S1470-2045(15)00613-0. Epub 2016 Mar 3.

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