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Abstract：
BACKGROUND: A combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC.
METHODS: This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis.
RESULTS: A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24-0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1-2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size.
CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study.
BACKGROUND: clinicaltrials.gov, NCT04118855.
METHODS: This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis.
RESULTS: A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24-0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1-2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size.
CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study.
BACKGROUND: clinicaltrials.gov, NCT04118855.
摘要：
背景：阿西替尼和免疫检查点抑制剂（ICIs）的组合在晚期肾细胞癌（RCC）的治疗中显示出有希望的疗效。本研究旨在前瞻性地评估其安全性，功效,和新辅助托里帕利马联合阿西替尼在非转移性透明细胞肾癌中的生物标志物。
方法：这是一个单一的机构，单臂II期临床试验。纳入具有非转移性活检证实的透明细胞RCC(T2-T3N0-1M0)的患者。患者将接受阿西替尼5mg，每天两次，每3周（三个周期）联合使用托里帕利马240mg，持续12周。然后，患者将在新辅助治疗后接受部分（PN）或根治性肾切除术（RN）。主要终点是客观反应率(ORR)。次要终点包括无病生存率，安全,围手术期并发症发生率。预测性生物标志物参与探索性分析。
结果：共有20名患者被纳入研究，其中19人正在接受手术。一名患者拒绝手术。主要终点ORR为45%。πORR的后验分布均值为0.44(95%可信区间:0.24-0.64)，满足预定义的主端点，ORR为32%。在肾切除术前，95％的患者观察到肿瘤缩小。此外，4例患者达到病理完全缓解.25%的患者发生≥3级不良事件，包括高血压,高血糖症,谷丙转氨酶/谷草转氨酶（ALT/AST）增加，和蛋白尿。术后,观察到1例4a级和8例1-2级并发症.与病情稳定的患者相比，应答者在精氨酸酶1（ARG1）等免疫因子上表现出显著差异，黑色素瘤抗原（MAGEs），树突状细胞(DC),TNF超家族成员13（TNFSF13），Apelin受体(APLNR),和C-C基序趋化因子配体3如1(CCL3-L1)。该试验的局限性在于样本量小。
结论：新佐剂托里帕利单抗联合阿西替尼在局部晚期透明细胞RCC中显示出令人鼓舞的活性和可接受的毒性，值得进一步研究。
背景：clinicaltrials.gov，NCT04118855。
方法：这是一个单一的机构，单臂II期临床试验。纳入具有非转移性活检证实的透明细胞RCC(T2-T3N0-1M0)的患者。患者将接受阿西替尼5mg，每天两次，每3周（三个周期）联合使用托里帕利马240mg，持续12周。然后，患者将在新辅助治疗后接受部分（PN）或根治性肾切除术（RN）。主要终点是客观反应率(ORR)。次要终点包括无病生存率，安全,围手术期并发症发生率。预测性生物标志物参与探索性分析。
结果：共有20名患者被纳入研究，其中19人正在接受手术。一名患者拒绝手术。主要终点ORR为45%。πORR的后验分布均值为0.44(95%可信区间:0.24-0.64)，满足预定义的主端点，ORR为32%。在肾切除术前，95％的患者观察到肿瘤缩小。此外，4例患者达到病理完全缓解.25%的患者发生≥3级不良事件，包括高血压,高血糖症,谷丙转氨酶/谷草转氨酶（ALT/AST）增加，和蛋白尿。术后,观察到1例4a级和8例1-2级并发症.与病情稳定的患者相比，应答者在精氨酸酶1（ARG1）等免疫因子上表现出显著差异，黑色素瘤抗原（MAGEs），树突状细胞(DC),TNF超家族成员13（TNFSF13），Apelin受体(APLNR),和C-C基序趋化因子配体3如1(CCL3-L1)。该试验的局限性在于样本量小。
结论：新佐剂托里帕利单抗联合阿西替尼在局部晚期透明细胞RCC中显示出令人鼓舞的活性和可接受的毒性，值得进一步研究。
背景：clinicaltrials.gov，NCT04118855。
