Canadian Cancer Trials Group, Queen's University, 10 Stuart Street, Kingston, ON, K7L3N6, Canada.
Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
Invest New Drugs. 2020 Oct;38(5):1442-1447. doi: 10.1007/s10637-020-00904-7. Epub 2020 Feb 4.
Background The IND.226 study was a phase Ib study to determine the recommended phase II dose of durvalumab + tremelimumab in combination with standard platinum-doublet chemotherapy. Sequential administration of multiple agents increases total chair time adding costs overall and inconvenience for patients. This cohort of the IND.226 study evaluated the safety and tolerability of durvalumab + tremelimumab given either sequentially (SEQ) or concurrently (CON). Methods Patients with advanced solid tumours were enrolled and randomised to either SEQ tremelimumab 75 mg IV over 1 h followed by durvalumab 1500 mg IV over 1 h q4wks on the same day, or CON administration over 1 h. The serum pharmacokinetic profile of SEQ versus CON of durvalumab and tremelimumab administration was also evaluated. Results 14 patients either received SEQ (n = 7pts) or CON (n = 7 pts). There were no infusion related reactions. Drug related adverse events (AEs) were mainly low grade and manageable, and comparable in frequency between SEQ/CON- fatigue (43%/57%), rash (43%/43%), pruritus (43%/29%) and nausea (14%/29%). One patient in each cohort discontinued treatment due to toxicity. The PK profiles of durvalumab and tremelimumab were similar between CON and SEQ, and to historical reference data. Conclusions Concurrent administration of durvalumab and tremelimumab over 1 h is safe with a comparable PK profile to sequential administration.
背景 IND.226 研究是一项 Ib 期研究，旨在确定 durvalumab+tremelimumab 联合标准铂类双重化疗的推荐 II 期剂量。序贯给予多种药物会增加总治疗时间，从而增加总体成本并给患者带来不便。IND.226 研究的这一组评估了序贯（SEQ）或同时（CON）给予 durvalumab+tremelimumab 的安全性和耐受性。
方法 招募了晚期实体瘤患者，并将其随机分配至 SEQ：tremelimumab 75mg IV 输注 1 小时，随后在同一天给予 durvalumab 1500mg IV 输注 1 小时，每 4 周 1 次；或 CON 治疗，输注 1 小时。还评估了 SEQ 与 CON 给药时 durvalumab 和 tremelimumab 的血清药代动力学特征。
结果 14 例患者接受了 SEQ（n=7 例）或 CON（n=7 例）治疗。没有输注相关反应。药物相关不良反应（AE）主要为低级别且可管理，并且在 SEQ/CON 组中频率相当：乏力（43%/57%）、皮疹（43%/43%）、瘙痒（43%/29%）和恶心（14%/29%）。每个队列中有 1 例患者因毒性而停止治疗。CON 和 SEQ 之间以及与历史参考数据相比，durvalumab 和 tremelimumab 的 PK 特征相似。
结论 1 小时内同时给予 durvalumab 和 tremelimumab 是安全的，其 PK 特征与序贯给药相当。
