Negrao Marcelo V, Papadimitrakopoulou Vassiliki A, Price Andrew C, Tam Alda L, Furqan Muhammad, Laroia Sandeep T, Massarelli Erminia, Pacheco Jose, Heymach John V, Tsao Anne S, Walker Gary V, Vora Lalit, Mauro David, Kelley Heather, Wooldridge James E, Krieg Arthur M, Niu Jiaxin
Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Radiology, Banner MD Anderson Cancer Center, Gilbert, Arizona.
JTO Clin Res Rep. 2022 Oct 26;4(3):100423. doi: 10.1016/j.jtocrr.2022.100423. eCollection 2023 Mar.
Vidutolimod, a CpG-A TLR9 agonist, was investigated in a phase 1b study (CMP-001-003; ClinicalTrials.gov, NCT03438318) in combination with atezolizumab with and without radiation therapy (RT) in patients with advanced NSCLC.
Patients with progressive disease after anti-programmed cell death protein 1 or programmed death-ligand 1 therapy received either vidutolimod and atezolizumab (part A) or vidutolimod, atezolizumab, and RT (part B). The primary objective was to evaluate the safety of vidutolimod and atezolizumab with and without RT. Key secondary end point was best objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1.
Between March 28, 2018, and July 25, 2019, a total of 29 patients were enrolled and received at least one dose of vidutolimod (part A, n = 13; part B, n = 16). Intratumoral injections of vidutolimod were administered successfully, including injection of visceral lesions. The most common treatment-related adverse events (≥30%) were flu-like symptoms and hypotension. No objective responses were observed; 23.1% and 50.0% of the patients in parts A and B, respectively, had stable disease as best response. In parts A and B, 15.4% and 25.0% of the patients, respectively, had tumor shrinkage (<30% decrease in tumor size, nonirradiated). Enrollment was stopped owing to lack of objective responses. In the two patients with initial tumor shrinkage in part A, a strong serum induction of C-X-C motif chemokine ligand 10 was observed.
Vidutolimod and atezolizumab with and without RT had a manageable safety profile, with minimal clinical activity in heavily pretreated patients with programmed cell death protein 1 or programmed death-ligand 1 blockade-resistant NSCLC.
维度利莫德是一种CpG-A TLR9激动剂，在一项1b期研究（CMP-001-003；ClinicalTrials.gov，NCT03438318）中，对晚期非小细胞肺癌（NSCLC）患者联合阿特珠单抗进行了研究，部分患者接受了放疗（RT），部分未接受。
抗程序性细胞死亡蛋白1或程序性死亡配体1治疗后病情进展的患者，接受维度利莫德和阿特珠单抗治疗（A部分）或维度利莫德、阿特珠单抗及放疗治疗（B部分）。主要目的是评估维度利莫德和阿特珠单抗联合或不联合放疗的安全性。关键次要终点是根据实体瘤疗效评价标准第1.1版评估的最佳客观缓解率。
2018年3月28日至2019年7月25日，共入组29例患者，均接受了至少一剂维度利莫德治疗（A部分13例；B部分16例）。维度利莫德瘤内注射成功实施，包括内脏病变注射。最常见的治疗相关不良事件（≥30%）为流感样症状和低血压。未观察到客观缓解；A部分和B部分分别有23.1%和50.0%的患者病情稳定为最佳缓解。A部分和B部分分别有15.4%和25.0%的患者出现肿瘤缩小（肿瘤大小缩小<30%，未接受放疗）。由于缺乏客观缓解，研究提前终止。在A部分最初出现肿瘤缩小的2例患者中，观察到血清C-X-C基序趋化因子配体10显著诱导。
维度利莫德联合或不联合放疗及阿特珠单抗安全性可控，但在接受过大量治疗的程序性细胞死亡蛋白1或程序性死亡配体1阻断耐药NSCLC患者中临床活性极小。
