Abstract：
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.
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.
摘要：
目的：Retifanlimab是针对程序性死亡1的人源化免疫球蛋白G4单克隆抗体，正在几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retifanlimab治疗的复发性微卫星不稳定性高（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；组织学证实/不可切除/复发，MSI-H/dMMR子宫内膜癌；检查点抑制剂初治）每4周静脉注射retifanlimab500mg，持续≤2年。主要终点是安全性/耐受性。
结果：在数据截止时（2023年5月17日），76名患者接受了至少一次retifanlimab剂量。中位（范围）年龄为67（49-88）岁；88.2％的患者患有复发性转移性疾病，80.3％的患者患有内脏转移。75例患者（98.7%）接受过至少一次全身治疗。retifanlimab暴露中位数为10.0（0.03-25.9）个月；23例患者完成治疗。38例患者（50.0%）有≥3级治疗紧急不良事件（TEAE），最常见的贫血（n=10[13.2%]）。63例患者（82.9%）有治疗相关的AE（TRAEs；≥3级，n=14[18.4%]）；最常见的是疲劳（n=14[18.4%]）。两名患者有导致死亡的TEAE；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％）的反应持续时间（DOR）≥12个月。中位随访时间26.0个月后未达到中位DOR。
结论：Retifanlimab在治疗前的复发性MSI-H/dMMR子宫内膜癌患者中通常具有良好的耐受性，并表现出令人鼓舞的抗肿瘤活性。
方法：符合条件的患者（≥18岁；组织学证实/不可切除/复发，MSI-H/dMMR子宫内膜癌；检查点抑制剂初治）每4周静脉注射retifanlimab500mg，持续≤2年。主要终点是安全性/耐受性。
结果：在数据截止时（2023年5月17日），76名患者接受了至少一次retifanlimab剂量。中位（范围）年龄为67（49-88）岁；88.2％的患者患有复发性转移性疾病，80.3％的患者患有内脏转移。75例患者（98.7%）接受过至少一次全身治疗。retifanlimab暴露中位数为10.0（0.03-25.9）个月；23例患者完成治疗。38例患者（50.0%）有≥3级治疗紧急不良事件（TEAE），最常见的贫血（n=10[13.2%]）。63例患者（82.9%）有治疗相关的AE（TRAEs；≥3级，n=14[18.4%]）；最常见的是疲劳（n=14[18.4%]）。两名患者有导致死亡的TEAE；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％）的反应持续时间（DOR）≥12个月。中位随访时间26.0个月后未达到中位DOR。
结论：Retifanlimab在治疗前的复发性MSI-H/dMMR子宫内膜癌患者中通常具有良好的耐受性，并表现出令人鼓舞的抗肿瘤活性。
