Sarah Cannon Research Institute, Nashville, TN, USA.
Tennessee Oncology, Nashville, TN, USA.
Oncologist. 2023 Jul 5;28(7):640-e559. doi: 10.1093/oncolo/oyad029.
This was an open-label, multicenter, single-arm phase Ib dose-escalation study of oral LCL161 administered in combination with oral topotecan in patients with relapsed/refractory small cell lung cancer (SCLC) and select gynecological cancers.
Cohorts of 3-6 patients initiated treatment with LCL161 and topotecan in escalating doses. LCL161 was administered orally on days 1, 8, and 15 of each 21-day cycle; topotecan was administered orally for the first 5 days of each 21-day cycle.
A total of 35 patients were enrolled in 6 cohorts; 30 patients were female; 4 patients had SCLC and 19 patients had ovarian cancer. Median prior lines of therapy were 3 (1-10). Median duration of treatment was 7.1 weeks (0.1-174). The most frequent grade 3/4 treatment-related adverse events were thrombocytopenia (51.43%) and anemia (31.43%). ORR was 9.7%; 58% of patients had SD. The study was stopped early before the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) were determined.
The addition of LCL161 to oral topotecan caused more myelosuppression when dosed together than what was associated with either drug alone. Moreover, the drug combination did not improve outcomes. The study was terminated early (ClinicalTrials.gov Identifier: NCT02649673).
这是一项开放标签、多中心、单臂 Ib 期剂量递增研究，评估口服 LCL161 联合口服拓扑替康治疗复发性/难治性小细胞肺癌（SCLC）和精选妇科癌症患者的疗效。
每 21 天周期的第 1、8 和 15 天给予 LCL161 和拓扑替康递增剂量，共 6 个队列，每个队列有 3-6 名患者入组。每 21 天周期的前 5 天给予拓扑替康口服治疗。
共纳入 35 名患者，入组 6 个队列；30 名患者为女性；4 名患者患有 SCLC，19 名患者患有卵巢癌。中位既往治疗线数为 3（1-10）。中位治疗持续时间为 7.1 周（0.1-174）。最常见的 3/4 级治疗相关不良事件为血小板减少（51.43%）和贫血（31.43%）。客观缓解率为 9.7%；58%的患者疾病稳定。在确定最大耐受剂量（MTD）和推荐的 II 期剂量（RP2D）之前，该研究提前终止。
LCL161 与口服拓扑替康联合使用时，骨髓抑制的发生率高于单独使用任何一种药物，且药物联合使用并未改善疗效。该研究提前终止（ClinicalTrials.gov 标识符：NCT02649673）。
