Abstract：
BACKGROUND: Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers.
METHODS: We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR).
RESULTS: Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response.
CONCLUSIONS: Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation.
BACKGROUND: Chinese Clinical Trial Registry, ChiCTR1900023277.
METHODS: We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR).
RESULTS: Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response.
CONCLUSIONS: Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation.
BACKGROUND: Chinese Clinical Trial Registry, ChiCTR1900023277.
摘要：
背景：先前的研究表明，在各种实体瘤中，将免疫检查点抑制剂与抗血管生成剂组合使用时，具有潜在的协同抗肿瘤活性。我们旨在评估卡姆瑞珠单抗（人源化程序性细胞死亡-1抗体）联合阿帕替尼（血管内皮生长因子受体酪氨酸激酶抑制剂）治疗晚期粘膜黑色素瘤（MM）患者的疗效和安全性。和探索相关的生物标志物。
方法：我们进行了单中心，开放标签，单臂,第二阶段研究。不可切除或复发/转移性MM患者接受卡利单抗和阿帕替尼治疗。主要终点是确认的客观反应率（ORR）。
结果：在2019年4月至2022年6月之间，共招募了32名患者，50.0%以前接受过全身治疗。在28例反应可评估的患者中，确认的ORR为42.9%，疾病控制率为82.1%,中位无进展生存期（PFS）为8.05个月。在未治疗和先前治疗的患者中，确认的ORR为42.9%(6/14)。值得注意的是,初治患者的中位PFS为11.89个月，接受过治疗的患者的中位PFS为6.47个月.3级治疗相关不良事件为转氨酶升高,皮疹,高胆红素血症,蛋白尿,高血压,血小板减少症,手足综合征和腹泻。没有观察到治疗相关的死亡。较高的肿瘤突变负荷（TMB），T细胞受体（TCR）多样性增加，受体酪氨酸激酶（RTK）/RAS途径的改变与更好的肿瘤反应相关。
结论：卡利珠单抗联合阿帕替尼在晚期MM患者中具有良好的抗肿瘤活性和可接受的毒性。TMB,TCR多样性和RTK/RAS途径基因被鉴定为潜在的预测性生物标志物，并需要进一步验证。
背景：中国临床试验注册中心，ChiCTR1900023277。
方法：我们进行了单中心，开放标签，单臂,第二阶段研究。不可切除或复发/转移性MM患者接受卡利单抗和阿帕替尼治疗。主要终点是确认的客观反应率（ORR）。
结果：在2019年4月至2022年6月之间，共招募了32名患者，50.0%以前接受过全身治疗。在28例反应可评估的患者中，确认的ORR为42.9%，疾病控制率为82.1%,中位无进展生存期（PFS）为8.05个月。在未治疗和先前治疗的患者中，确认的ORR为42.9%(6/14)。值得注意的是,初治患者的中位PFS为11.89个月，接受过治疗的患者的中位PFS为6.47个月.3级治疗相关不良事件为转氨酶升高,皮疹,高胆红素血症,蛋白尿,高血压,血小板减少症,手足综合征和腹泻。没有观察到治疗相关的死亡。较高的肿瘤突变负荷（TMB），T细胞受体（TCR）多样性增加，受体酪氨酸激酶（RTK）/RAS途径的改变与更好的肿瘤反应相关。
结论：卡利珠单抗联合阿帕替尼在晚期MM患者中具有良好的抗肿瘤活性和可接受的毒性。TMB,TCR多样性和RTK/RAS途径基因被鉴定为潜在的预测性生物标志物，并需要进一步验证。
背景：中国临床试验注册中心，ChiCTR1900023277。
