Berton Dominique, Pautier Patricia, Lorusso Domenica, Gennigens Christine, Gladieff Laurence, Kryzhanivska Anna, Bowman Jill, Tian Chuan, Cornfeld Mark, Van Gorp Toon
GINECO & Institut de Cancérologie de l'Ouest (ICO), Centre René Gauducheau, Saint-Herblain, France.
Gustave-Roussy, Villejuif, France.
Gynecol Oncol. 2024 Jul;186:191-198. doi: 10.1016/j.ygyno.2024.05.025. Epub 2024 Jun 1.
Retifanlimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 being investigated in several solid tumor types. We report final results from patients with recurrent microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer treated with retifanlimab in a POD1UM-101 expansion cohort.
Eligible patients (≥18 years; histologically proven/unresectable/recurrent, MSI-H/dMMR endometrial cancer; checkpoint inhibitor naive) received retifanlimab 500 mg intravenously every 4 weeks for ≤2 years. Primary endpoint was safety/tolerability.
At data cutoff (May 17, 2023), 76 patients had received at least one retifanlimab dose. Median (range) age was 67 (49-88) years; 88.2% of patients had recurrent metastatic disease and 80.3% had visceral metastases. Seventy-five patients (98.7%) had received at least one prior systemic therapy. Median retifanlimab exposure was 10.0 (0.03-25.9) months; 23 patients completed treatment. 38 patients (50.0%) had grade ≥3 treatment-emergent adverse events (TEAEs), most commonly anemia (n = 10 [13.2%]). 63 patients (82.9%) had treatment-related AEs (TRAEs; grade ≥3, n = 14 [18.4%]); most common was fatigue (n = 14 [18.4%]). Two patients had TEAEs that led to death; no TRAEs were fatal. 39 patients had objective responses (51.3%; 95% CI, 39.6-63.0%); 19 patients (25.0%) had complete response and 20 (26.3%) had partial response. Median progression-free survival was 12.2 months; 30 patients (76.9%) had duration of response (DOR) ≥12 months. Median DOR was not reached after median follow-up time of 26.0 months.
Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer.
瑞替凡利单抗是一种抗程序性死亡1的人源化免疫球蛋白G4单克隆抗体，正在多种实体瘤类型中进行研究。我们报告了在POD1UM - 101扩展队列中接受瑞替凡利单抗治疗的复发性微卫星高度不稳定（MSI-H）/错配修复缺陷（dMMR）子宫内膜癌患者的最终结果。
符合条件的患者（≥18岁；组织学确诊/不可切除/复发性MSI-H/dMMR子宫内膜癌；未接受过检查点抑制剂治疗）每4周静脉注射500 mg瑞替凡利单抗，持续≤2年。主要终点是安全性/耐受性。
在数据截止（2023年5月17日）时，76例患者至少接受过一剂瑞替凡利单抗。中位（范围）年龄为67（49 - 88）岁；88.2%的患者有复发性转移性疾病，80.3%有内脏转移。75例患者（98.7%）至少接受过一种先前的全身治疗。瑞替凡利单抗的中位暴露时间为10.0（0.03 - 25.9）个月；23例患者完成治疗。38例患者（50.0%）发生≥3级治疗中出现的不良事件（TEAE），最常见的是贫血（n = 10 [13.2%]）。63例患者（82.9%）发生与治疗相关的不良事件（TRAE；≥3级，n = 14 [18.4%]）；最常见的是疲劳（n = 14 [18.4%]）。2例患者的TEAE导致死亡；没有TRAE是致命的。39例患者有客观反应（51.3%；95% CI，39.6 - 63.0%）；19例患者（25.0%）完全缓解，20例（26.3%）部分缓解。中位无进展生存期为12.2个月；30例患者（76.9%）缓解持续时间（DOR）≥12个月。在中位随访时间26.0个月后，中位DOR未达到。
瑞替凡利单抗总体耐受性良好，在先前接受过治疗的复发性MSI-H/dMMR子宫内膜癌患者中显示出令人鼓舞的抗肿瘤活性。
