Long Georgina V, Ferrucci Pier Francesco, Khattak Adnan, Meniawy Tarek M, Ott Patrick Alexander, Chisamore Michael, Trolle Thomas, Hyseni Agon, Heegaard Erik
Melanoma Institute Australia, The University of Sydney, & Royal North Shore & Mater Hospitals, Sydney, New South Wales, 2065, Australia.
Cancer Biotherapy Unit, Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, 20139, Italy.
Future Oncol. 2022 Oct;18(31):3473-3480. doi: 10.2217/fon-2022-0694. Epub 2022 Sep 1.
Despite improvements made with checkpoint inhibitor (CPI) therapy, a need for new approaches to improve outcomes for patients with unresectable or metastatic melanoma remains. EVX-01, a personalized neoepitope vaccine, combined with pembrolizumab treatment, holds the potential to fulfill this need. Here we present the rationale and novel design behind the KEYNOTE - D36 trial: an open label, single arm, phase II trial aiming to establish the clinical proof of concept and evaluate the safety of EVX-01 in combination with pembrolizumab in CPI naive patients with unresectable or metastatic melanoma. The primary objective is to evaluate if EVX-01 improves best overall response after initial stable disease or partial response to pembrolizumab treatment, in patients with advanced melanoma. The novel end points ensure a decisive readout which may prove helpful before making major investments in phase III trials with limited phase I data. : NCT05309421 (ClinicalTrials.gov).
尽管检查点抑制剂（CPI）疗法已取得进展，但仍需要新的方法来改善不可切除或转移性黑色素瘤患者的治疗效果。个性化新抗原疫苗EVX-01与帕博利珠单抗联合治疗，有望满足这一需求。在此，我们介绍了KEYNOTE-D36试验背后的基本原理和新颖设计：一项开放标签、单臂、II期试验，旨在确立临床概念验证，并评估EVX-01与帕博利珠单抗联合应用于初治CPI的不可切除或转移性黑色素瘤患者的安全性。主要目标是评估在晚期黑色素瘤患者中，EVX-01是否能在最初病情稳定或对帕博利珠单抗治疗出现部分缓解后改善最佳总体缓解。这些新颖的终点确保了决定性的结果判定，这在基于有限的I期数据进行III期试验的重大投资之前可能会有所帮助。试验注册号：NCT05309421（ClinicalTrials.gov）
