Objectives

Combined therapy should be invested for those patients who are refractory to first-line therapy. Anti-angiogenic agents could enhance tumor immunity response. We designed a phase IB clinical trial and analyzed the effectiveness and safety of anlotinib combined with PD-1inhibitors Camrelizumab for multi-line pretreated and failed advanced NSCLC to explore the synergistic effect of anti-angiogenic agents and immunotherapy.

Methods

All enrolled patients should receive camrelizumab 200 mg every 3 weeks. Eligible patients were randomized successively to three dose cohorts of Anlotinib in a dose escalation clinical setting. Once maximal tolerable dose was established, the primary end point of this study was progression-free survival, overall survival and safety. Risk factor was an exploratory end point.

Results

The identified expansion dose for anlotinib was 12mg. The median PFS of ITT patients was 8.2 months (95% CI, 4.3–12.1 months). And the mOS was 12.7months (95% CI, 10.2–15.1 months). There was significant difference of mPFS between the 8mg cohort and the 12mg cohort (5.6m vs.11.0m, p=0.04). Patients with brain metastasis had a significantly higher risk of death (HR 5.90; 95% CI 2.01–17.30; P = 0.001). Patients whose ECOG was 0 and 1 had a significantly lower risk of death (HR 0.36; 95% CI 0.14–0.91; P = 0.031).

Conclusions

Anlotinib plus camrelizumab had shown promising efficacy and manageable toxicity as a second-line or later-line treatment for NSCLCs, especially in the 12mg cohorts. Large-scale phase III clinical trials are needed to further explore the rational combination models and biomarkers.

中文翻译：

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安罗替尼联合抗 PD-1 抗体、camrelizumab 治疗晚期 NSCLC 多线治疗后：一项开放标签、剂量递增和扩展研究

目标

对一线治疗无效的患者应进行联合治疗。抗血管生成剂可以增强肿瘤免疫反应。我们设计了一项 IB 期临床试验，分析了安罗替尼联合 PD-1 抑制剂 Camrelizumab 用于多线预处理和失败的晚期 NSCLC 的有效性和安全性，以探索抗血管生成药物和免疫治疗的协同作用。

方法

所有入组患者均应每 3 周接受 200 mg 卡瑞利珠单抗治疗。符合条件的患者在剂量递增临床环境中连续随机分配到三个安罗替尼剂量组。一旦确定了最大耐受剂量，本研究的主要终点是无进展生存期、总生存期和安全性。风险因素是一个探索性终点。

结果

安罗替尼的确定扩展剂量为 12mg。ITT 患者的中位 PFS 为 8.2 个月（95% CI，4.3-12.1 个月）。mOS 为 12.7 个月（95% CI，10.2-15.1 个月）。8mg 组和 12mg 组的 mPFS 存在显着差异（5.6m vs.11.0m，p=0.04）。脑转移患者的死亡风险显着升高（HR 5.90；95% CI 2.01–17.30；P = 0.001）。ECOG 为 0 和 1 的患者死亡风险显着降低（HR 0.36；95% CI 0.14-0.91；P = 0.031）。

结论

安罗替尼联合卡瑞利珠单抗作为 NSCLC 的二线或后线治疗显示出有希望的疗效和可控的毒性，尤其是在 12mg 队列中。需要进行大规模的III期临床试验，进一步探索合理的组合模型和生物标志物。