PD-1抑制剂瑞替凡利单抗在复发的微卫星高度不稳定或错配修复缺陷子宫内膜癌患者中的抗肿瘤活性和安全性：POD1UM-101 I期研究队列H的最终安全性和疗效结果
Antitumor activity and safety of the PD-1 inhibitor retifanlimab in patients with recurrent microsatellite instability-high or deficient mismatch repair endometrial cancer: Final safety and efficacy results from cohort H of the POD1UM-101 phase I study.
作者信息
Berton Dominique, Pautier Patricia, Lorusso Domenica, Gennigens Christine, Gladieff Laurence, Kryzhanivska Anna, Bowman Jill, Tian Chuan, Cornfeld Mark, Van Gorp Toon
机构信息
GINECO & Institut de Cancérologie de l'Ouest (ICO), Centre René Gauducheau, Saint-Herblain, France.
Gustave-Roussy, Villejuif, France.
出版信息
Gynecol Oncol. 2024 Jul;186:191-198. doi: 10.1016/j.ygyno.2024.05.025. Epub 2024 Jun 1.
OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer.
目的
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。
方法
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。
结果
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。
结论
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。
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