Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles Medical Center, David Geffen School of Medicine, 2825 Santa Monica Blvd., Suite 200, Santa Monica, Los Angeles, CA, 90404-2429, USA.
Asan Medical Centre, University of Ulsan College of Medicine, Seoul, South Korea.
Gastric Cancer. 2024 May;27(3):558-570. doi: 10.1007/s10120-024-01466-w. Epub 2024 Feb 3.
We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2-negative gastric or gastroesophageal junction cancer (GC).
Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months.
In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval [CI]) was 9.5 months (7.3-13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7-8.4) with placebo-mFOLFOX6 (hazard ratio [HR], 0.72; 95% CI 0.49-1.08); median OS (95% CI) was 19.2 (13.6-24.2) and 13.5 (9.3-15.9) months, respectively (HR 0.77; 95% CI 0.52-1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26-0.73); OS: HR 0.52 (95% CI 0.31-0.85). No new safety findings were reported.
In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626).
NCT03694522.
我们报告了随机 2 期 FIGHT 试验的最终结果，该试验评估了贝马鲁单抗（一种针对成纤维细胞生长因子受体 2b（FGFR2b）的人源化单克隆抗体）联合 mFOLFOX6 治疗 FGFR2b 阳性（免疫组织化学 2+ / 3+ 膜染色）、HER-2 阴性胃或胃食管交界处癌（GC）患者。
患者接受贝马鲁单抗（15mg/kg）或安慰剂每 2 周一次，第 1 周期第 8 天额外给予贝马鲁单抗（7.5mg/kg）或安慰剂。所有患者均接受 mFOLFOX6 治疗。主要终点为研究者评估的无进展生存期（PFS）。次要终点包括总生存期（OS）、客观缓解率和安全性。在至少 24 个月的随访后评估疗效。
在贝马鲁单抗-mFOLFOX6（N=77）和安慰剂-mFOLFOX6（N=78）组中，分别有 59.7%和 66.7%的患者肿瘤细胞中 FGFR2b 阳性（≥10%）。贝马鲁单抗-mFOLFOX6 组的中位 PFS（95%CI）为 9.5 个月（7.3-13.7），安慰剂-mFOLFOX6 组为 7.4 个月（5.7-8.4）（HR，0.72；95%CI，0.49-1.08）；中位 OS（95%CI）分别为 19.2（13.6-24.2）和 13.5（9.3-15.9）个月（HR，0.77；95%CI，0.52-1.14）。在肿瘤细胞中 FGFR2b 阳性（≥10%）的 GC 中观察到的疗效为：PFS：HR 0.43（95%CI，0.26-0.73）；OS：HR 0.52（95%CI，0.31-0.85）。未报告新的安全性发现。
在 FGFR2b 阳性的晚期 GC 中，贝马鲁单抗-mFOLFOX6 联合治疗与单独使用 mFOLFOX6 相比，中位 PFS 和 OS 均有延长。在 FGFR2b 过表达（≥10%的肿瘤细胞）时，疗效更为显著。正在进行确证性 3 期试验（NCT05052801，NCT05111626）。
NCT03694522。
