Norman Aurora, Seetharam Mahesh, Allred Jacob, Kong Jianping, Opyrchal Mateusz, Ma Wen Wee, Lou Yanyan, Dy Grace K, Mahipal Amit, Weroha S John, Wahner Hendrickson Andrea E, Reid Joel M, Adjei Alex A
Mayo Clinic, Rochester, MN, USA.
Mayo Clinic, Phoenix, AZ, USA.
BJC Rep. 2025 Jan 14;3(1):1. doi: 10.1038/s44276-024-00107-0.
Based on preclinical data showing addition of CDK4/6 inhibitors to gemcitabine was synergistic, ribociclib was evaluated in combination with gemcitabine to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).
In this single arm multicohort phase I trial, we evaluated the safety and efficacy of ribociclib plus gemcitabine in patients with advanced solid tumors. Patients received gemcitabine intravenously on days 1 and 8 followed by ribociclib days 8-14, with treatment repeated every 3 weeks.
The study enrolled 43 patients between October 2017 and September 2019. The escalation phase (19 patients) determined the MTD and recommended phase II dose (RP2D) to be ribociclib 800 mg daily and gemcitabine 1000 mg/m2 for the expansion phase (24 patients). One patient experienced Grade 4 thrombocytopenia. Eleven patients experienced Grade 3 adverse events (AE), the most common being neutropenia, thrombocytopenia, and anemia. No partial or complete responses were observed. 15/22 (68%) of efficacy evaluable patients who received the MTD achieved best response of stable disease.
The addition of ribociclib to gemcitabine was tolerated well and yielded stability of tumors in both cohorts. Biomarkers such as Rb status and activity of CDK2 and CDK4/6 complexes may help to select patients who may respond better to the combination of gemcitabine and ribociclib.
NCT03237390.
基于临床前数据显示，在吉西他滨中添加CDK4/6抑制剂具有协同作用，因此对瑞博西尼与吉西他滨联合用药进行了评估，以确定最大耐受剂量（MTD）和剂量限制性毒性（DLT）。
在这项单臂多队列I期试验中，我们评估了瑞博西尼联合吉西他滨治疗晚期实体瘤患者的安全性和疗效。患者在第1天和第8天静脉注射吉西他滨，随后在第8 - 14天服用瑞博西尼，每3周重复治疗。
该研究在2017年10月至2019年9月期间招募了43名患者。剂量递增阶段（19名患者）确定MTD和推荐的II期剂量（RP2D）为瑞博西尼每日800mg，吉西他滨1000mg/m²用于扩展阶段（24名患者）。1名患者出现4级血小板减少症。11名患者出现3级不良事件（AE），最常见的是中性粒细胞减少、血小板减少和贫血。未观察到部分或完全缓解。接受MTD的22名可评估疗效患者中有15名（68%）达到疾病稳定的最佳反应。
在吉西他滨中添加瑞博西尼耐受性良好，且在两个队列中均使肿瘤稳定。诸如Rb状态以及CDK2和CDK4/6复合物活性等生物标志物可能有助于选择对吉西他滨和瑞博西尼联合用药反应更好的患者。
NCT03237390。
