BackgroundCombination of chidamide and anti‐PD‐L1 inhibitor produce synergistic anti‐tumor effect in advanced NSCLC patients resistant to anti‐PD‐1 treatment. However, the effect of chidamide plus envafolimab has not been reported.AimsThis study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti‐PD‐1 treatment.Materials and MethodsEligible advanced NSCLC patients after resistant to anti‐PD‐1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression‐free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD‐L1, and blood TMB (bTMB) was also analyzed.ResultsAfter a median follow‐up of 8.1 (range: 7.6–9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9–5.5) months. Biomarker analysis revealed that patients with high‐level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD‐L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low‐level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable.DiscussionHigh HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD‐L1 and low‐level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion.ConclusionCombination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

中文翻译：

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西达本胺加 envafolimab 作为抗 PD-1 治疗耐药的晚期非小细胞肺癌患者的后续治疗：一项多队列、开放标签、生物标志物分析的 II 期试验

背景西达本胺与抗PD-L1抑制剂联合治疗对抗PD-1治疗耐药的晚期NSCLC患者产生协同抗肿瘤作用。然而，西达本胺联合envafolimab的效果尚未见报道。目的本研究旨在评估西达本胺联合envafolimab治疗抗PD-1耐药的晚期NSCLC患者的疗效。材料与方法符合条件的抗PD-1耐药后的晚期NSCLC患者治疗采用西达本胺和 envafolimab。主要终点是客观缓解率（ORR）。次要终点包括疾病控制率（DCR）、无进展生存期（PFS）和安全性。还分析了组蛋白脱乙酰酶 2 (HDAC2)、PD-L1 和血液 TMB (bTMB) 的表达。结果在中位随访 8.1 个月（范围：7.6-9.2）个月后，只有两名患者获得部分缓解。 ORR 为 6.7% (2/30)，DCR 为 50% (15/30)，中位 PFS (mPFS) 为 3.5 个月（95% 置信区间：1.9-5.5）个月。生物标志物分析显示，HDAC2 高水平表达的患者具有较高的 ORR（4.3% vs. 0）、DCR（52.2% vs. 0）和 mPFS（3.7 vs. 1.4m）。 PD-L1 阴性患者的 DCR（52.2% vs. 33.3%）和 mPFS（3.7m vs. 1.8m）在数值上较高，bTMB 水平较低的患者也是如此（DCR：59.1% vs. 16.7%，mPFS：3.8） vs.1.9m）。总体安全性可控。讨论高HDAC2患者表现出更好的ORR、DCR和PFS。此外，PD-L1 阴性且 bTMB 水平较低的患者具有更好的 DCR 和 PFS。这可能与西达本胺的表观遗传功能有关。但样本量不够大，需要增加样本量来证实这一结论。结论西达本胺联合恩伐利单抗在某些NSCLC患者中显示出疗效信号。但进一步识别有益人群对于精准治疗是必要的。