一项1期、儿童首例、多中心研究，旨在评估溶瘤性疱疹病毒talimogene laherparepvec在晚期实体瘤儿科患者中的安全性和疗效。
A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors.
作者信息
Moreno Lucas, Teira Pierre, Croop James M, Gerber Nicolas U, André Nicolas, Aerts Isabelle, Gros Subias Luis, De Wilde Bram, Bautista Francisco, Turpin Brian, Kunduri Srinivasa, Hamidi Ali, Lawrence Tatiana, Streby Keri A
机构信息
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada.
出版信息
Front Pediatr. 2023 May 24;11:1183295. doi: 10.3389/fped.2023.1183295. eCollection 2023.
BACKGROUND
The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors.
METHODS
T-VEC was delivered by intralesional injection at 10 plaque-forming units (PFU)/ml on the first day, followed by 10 PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST).
RESULTS
Fifteen patients were enrolled into two cohorts based on age: cohort A1 ( = 13) 12 to ≤21 years old (soft-tissue sarcoma, = 7; bone sarcoma, = 3; neuroblastoma, = 1; nasopharyngeal carcinoma, = 1; and melanoma, = 1) and cohort B1 ( = 2) 2 to <12 years old (melanoma, = 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response.
CONCLUSIONS
T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02756845. https://clinicaltrials.gov/ct2/show/NCT02756845.
背景
复发和难治性肿瘤患儿的生存率很低。目前缺乏成功的治疗策略，这些患者对新型疗法仍有未满足的需求。我们在此报告了一项关于talimogene laherparepvec（T-VEC）的1期研究结果，并探讨了这种溶瘤免疫疗法治疗晚期非中枢神经系统肿瘤患儿的安全性。
方法
T-VEC于第1天通过瘤内注射给药，剂量为10个空斑形成单位（PFU）/ml，随后在第4周的第1天及此后每2周给药一次，剂量为10 PFU/ml。主要目标是根据剂量限制性毒性（DLT）的发生率评估安全性和耐受性。次要目标包括根据模拟实体瘤疗效评价标准（irRC-RECIST）的改良免疫相关反应标准所显示的反应和生存情况来评估疗效。
结果
15名患者根据年龄被纳入两个队列：队列A1（n = 13），年龄在12至≤21岁之间（软组织肉瘤，n = 7；骨肉瘤，n = 3；神经母细胞瘤，n = 1；鼻咽癌，n = 1；黑色素瘤，n = 1）；队列B1（n = 2），年龄在2至<12岁之间（黑色素瘤，n = 2）。总体而言，患者接受治疗的中位（范围）时间为5.1（0.1，39.4）周。在评估期间未观察到DLT。所有患者均经历了至少一次治疗中出现的不良事件（TEAE），53.3%的患者报告了≥3级TEAE。总体而言，86.7%的患者报告了与治疗相关的TEAE。未观察到完全缓解或部分缓解，3名患者（20%）总体上表现为疾病稳定，这是最佳反应。
结论
通过未观察到DLT评估，T-VEC是可耐受的。安全性数据与患者潜在的癌症情况以及T-VEC在成人研究中的已知安全性概况一致。未观察到客观反应。
试验注册
ClinicalTrials.gov：NCT02756845。https://clinicaltrials.gov/ct2/show/NCT02756845。
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