Table1_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.pdf

BackgroundThe 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.
MethodsT-VEC was delivered by intralesional injection at 106 plaque-forming units (PFU)/ml on the first day, followed by 108 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).
ResultsFifteen patients were enrolled into two cohorts based on age: cohort A1 (n = 13) 12 to ≤21 years old (soft-tissue sarcoma, n = 7; bone sarcoma, n = 3; neuroblastoma, n = 1; nasopharyngeal carcinoma, n = 1; and melanoma, n = 1) and cohort B1 (n = 2) 2 to <12 years old (melanoma, n = 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.
ConclusionsT-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 RegistrationClinicalTrials.gov: NCT02756845. https://clinicaltrials.gov/ct2/show/NCT02756845.

背景：复发难治性肿瘤儿科患者的生存率普遍较低，目前尚无成熟有效的治疗策略，此类患者仍存在新型治疗手段的未被满足的临床需求。本研究报告了Talimogene Laherparepvec（T-VEC）的I期临床试验结果，并探讨该溶瘤免疫疗法用于治疗晚期非中枢神经系统肿瘤儿科患者的安全性。

方法：T-VEC采用瘤内注射给药：首日给予10⁶噬斑形成单位（PFU）/mL，第4周首日及此后每2周给予10⁸ PFU/mL。本研究的主要终点为通过剂量限制性毒性（DLTs）发生率评估的安全性与耐受性。次要终点包括采用模拟实体瘤疗效评价标准的免疫相关疗效评价标准（irRC-RECIST）评估的疗效，以应答情况与生存获益作为疗效评价指标。

结果：本研究共纳入15例患者，按年龄分为两个队列：队列A1（n=13）为12岁至≤21岁患者，其中软组织肉瘤7例、骨肉瘤3例、神经母细胞瘤1例、鼻咽癌1例、黑色素瘤1例；队列B1（n=2）为2岁至<12岁患者，均为黑色素瘤。整体而言，患者的中位治疗时长为5.1周（范围：0.1~39.4周）。评估期间未观察到剂量限制性毒性。所有患者均出现至少1例治疗突发不良事件（TEAE），其中53.3%的患者报告了≥3级治疗突发不良事件，86.7%的患者报告了治疗相关不良事件。本研究未观察到完全缓解或部分缓解，共有3例患者（占比20%）的最佳疗效为疾病稳定。

结论：本研究未观察到剂量限制性毒性，提示T-VEC具有良好的耐受性。安全性数据与患者基础癌症情况及成人人群研究中T-VEC的已知安全性特征一致。本研究未观察到客观抗肿瘤应答。

试验注册：ClinicalTrials.gov编号：NCT02756845。https://clinicaltrials.gov/ct2/show/NCT02756845。