Phase I Dose-Escalation Study of the Dual PI3K-mTORC1/2 Inhibitor Gedatolisib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors
Phase I Dose-Escalation Study of the Dual PI3K-mTORC1/2 Inhibitor Gedatolisib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors
复制标题
DOI：
10.1158/1078-0432.ccr-21-1402
复制
发表时间：
2021-09-15
影响因子：
11.5
通讯作者：
Stathis, Anastasios
中科院分区：
文献类型：
--
作者：
Colombo, Ilaria;Genta, Sofia;Stathis, Anastasios
目的：本I期研究评估PI3K/mTORC1/2双抑制剂gedatolisib联合卡铂和紫杉醇的安全性、耐受性、药代动力学和初步活性。患者和方法：晚期实体瘤患者在第1周期接受75%的gedatolisib治疗。II期推荐剂量为gedatolisib 110 mg，第1、8、15和22天，卡铂AUC5第1天，紫杉醇80 mg/m(2)第1、8和15天。最常见的>= G3治疗相关不良事件是中性粒细胞减少症（35%）、贫血（18%）和粘膜炎（12%）。总有效率为65% （CCOC为80%）。马托利布的药动学参数与单药结果一致。结论：吉托利昔联合卡铂、紫杉醇治疗是可耐受的，且对CCOC有初步疗效。
Purpose: This phase I study evaluated safety, tolerability, pharmacokinetics, and preliminary activity of the PI3K/mTORC1/2 dual inhibitor gedatolisib combined with carboplatin and paclitaxel.Patients and Methods: Patients with advanced solid tumors treated with = 75% of gedatolisib at cycle 1). The recommended phase II dose is gedatolisib 110 mg on days 1, 8, 15, and 22 with carboplatin AUC5 on day 1 and paclitaxel 80 mg/m(2) on days 1, 8, and 15. The most frequent >= G3 treatment-related adverse events were neutropenia (35%), anemia (18%), and mucositis (12%). The overall response rate was 65% (80% in CCOC). Pharmacokinetic parameters of gedatolisib were consistent with single-agent results.Conclusions: Gedatolisib combined with carboplatin and paclitaxel is tolerable, and preliminary efficacy was observed especially in CCOC.