Background. TACE may prime adaptive immunity and enhance immunotherapy efficacy. PETAL evaluated safety, preliminary activity of TACE plus pembrolizumab and explored mechanisms of efficacy. Methods. Patients with liver-confined HCC were planned to receive up to 2 rounds of TACE followed by pembrolizumab 200 mg every 21 days commencing 30-days post-TACE until disease progression or unacceptable toxicity for up to 1 year. Primary endpoint was safety, 21-days dose-limiting toxicities (DLT) from pembrolizumab initiation. Secondary endpoints included progression-free survival (PFS) and evaluation of tumour and host determinants of response. Results. Fifteen patients were included in the safety and efficacy population: 73% had non-viral cirrhosis, median age was 72 years. Child-Pugh (CP) class was A in 14 patients. Median tumour size was 4 cm. Ten patients (67%) received pembrolizumab after 1 TACE, 5 patients after 2 (33%). Pembrolizumab yielded no synergistic toxicity nor DLTs post-TACE. Treatment-related adverse events occurred in 93% of patients most commonly skin rash (40%), fatigue and diarrhoea (27%). After a median follow-up of 38.5 months, objective response rate (ORR) 12 weeks post-TACE was 53%. PFS rate at 12 weeks was 93% and median PFS was 8.95 months (95%CI 7.30-NA). Median duration of response was 7.3 months (95%CI: 6.3-8.3). Median OS was 33.5 months (95%CI: 11.6-NA). Dynamic changes in peripheral T-cell subsets, circulating tumour DNA, serum metabolites and in stool bacterial profiles highlight potential mechanisms of action of multi-modal therapy. Conclusions. TACE plus pembrolizumab was tolerable with no evidence of synergistic toxicity, encouraging further clinical development of immunotherapy alongside TACE.

中文翻译：

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肝细胞癌经动脉化疗栓塞术后派姆单抗的安全性和初步疗效：PETAL Ib 期研究。

背景。 TACE 可以启动适应性免疫并增强免疫治疗效果。 PETAL 评估了 TACE 联合派姆单抗的安全性、初步活性并探讨了疗效机制。方法。肝局限性 HCC 患者计划接受最多 2 轮 TACE，随后从 TACE 后 30 天开始每 21 天接受一次派姆单抗 200 mg，直至疾病进展或出现不可接受的毒性，持续长达 1 年。主要终点是安全性、派姆单抗起始后的 21 天剂量限制毒性 (DLT)。次要终点包括无进展生存期（PFS）以及肿瘤和宿主反应决定因素的评估。结果。安全性和有效性人群中纳入了 15 名患者：73% 患有非病毒性肝硬化，中位年龄为 72 岁。 14 名患者的 Child-Pugh (CP) 分级为 A。肿瘤大小中位数为 4 厘米。 10 名患者 (67%) 在 1 次 TACE 后接受派姆单抗治疗，5 名患者在 2 次 TACE 后接受帕博利珠单抗治疗 (33%)。 Pembrolizumab 在 TACE 后未产生协同毒性或 DLT。 93% 的患者发生了与治疗相关的不良事件，最常见的是皮疹 (40%)、疲劳和腹泻 (27%)。中位随访 38.5 个月后，TACE 后 12 周的客观缓解率 (ORR) 为 53%。 12 周时的 PFS 率为 93%，中位 PFS 为 8.95 个月 (95%CI 7.30-NA)。中位缓解持续时间为 7.3 个月（95%CI：6.3-8.3）。中位 OS 为 33.5 个月（95% CI：11.6-NA）。外周T细胞亚群、循环肿瘤DNA、血清代谢物和粪便细菌谱的动态变化凸显了多模式治疗的潜在作用机制。结论。 TACE 加派姆单抗具有耐受性，没有证据表明存在协同毒性，这鼓励了 TACE 联合免疫治疗的进一步临床开发。