曲美替尼
彭布罗利珠单抗
加药
医学
不利影响
内科学
黑色素瘤
肿瘤科
免疫疗法
MAPK/ERK通路
生物
癌症
癌症研究
激酶
细胞生物学
作者
Michele Maio,Matteo S. Carlino,Anthony M. Joshua,Elaine McWhirter,Antoni Ribas,Paolo A. Ascierto,Wilson H. Miller,Marcus O. Butler,Pier Francesco Ferrucci,Robert Zielinski,Michele Del Vecchio,Eduard Gasal,Razi Ghori,Scott J. Diede,Elizabeth Croydon,Omid Hamid
标识
DOI:10.1016/j.ejca.2021.09.024
摘要
Parts 4 and 5 of the phase 1/2 KEYNOTE-022 study investigated the maximum tolerated dose (MTD), safety, and efficacy of pembrolizumab plus trametinib in solid tumours and BRAF wild-type melanoma.Patients received intermittent or concurrent dosing of pembrolizumab plus trametinib. Concurrent dosing was 2 or 4 weeks of trametinib run-in followed by concurrent pembrolizumab every 3 weeks (Q3W) plus trametinib once daily (QD). Intermittent dosing was 2 weeks of trametinib run-in followed by pembrolizumab plus intermittent trametinib (1 week off/2 weeks on). A 3 + 3 dose escalation was used, followed by dose confirmation.Forty-two patients were enrolled. No dose-limiting toxicities (DLTs) occurred at initial dose levels (DL). At subsequent DLs, 10 of 38 evaluable patients had DLTs. For concurrent dosing, MTD was pembrolizumab 200 mg Q3W plus trametinib 1.5 mg QD, with a 2-week trametinib 1.5 mg QD run-in (concurrent DL2a); in concurrent DL2a group, five (31%) patients had grade 3/4 treatment-related adverse events (TRAEs); the objective response rate (ORR) was 0%. ORR was 40% in concurrent DL1 and 0% in concurrent DL2b. For intermittent dosing, MTD was pembrolizumab 200 mg Q3W plus trametinib 2 mg QD with a 2-week trametinib 2 mg QD run-in (intermittent DL2); in the intermittent DL2 group, seven (47%) patients had grade 3/4 TRAEs; ORR was 27%. ORR in intermittent DL1 was 33%.MTDs for concurrent and intermittent dosing of pembrolizumab with trametinib were identified. The combination had limited antitumour activity, numerically higher ORR with intermittent versus concurrent dosing, and manageable safety. CLINICALTRIALS.NCT02130466.
科研通智能强力驱动
Strongly Powered by AbleSci AI