Abstract：
OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
CONCLUSIONS: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can\'t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.
METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
CONCLUSIONS: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can\'t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.
摘要：
目的：QL1604是一种高度选择性的，针对程序性死亡蛋白1的人源化单克隆抗体.我们评估了QL1604联合化疗作为晚期宫颈癌患者一线治疗的疗效和安全性。
方法：这是一个多中心，开放标签，单臂,第二阶段研究。在每个21天周期的第1天，招募未接受过全身化疗的晚期宫颈癌患者，接受QL1604联合紫杉醇和顺铂/卡铂，为期6个周期。其次是QL1604维持治疗。
结果：纳入46例患者，中位随访时间为16.5个月。84.8%的患者患有复发性疾病，13.0%的患者患有IVB期疾病。根据晚期实体瘤（RECIST）v1.1的疗效评估标准，客观缓解率（ORR）为58.7％（27/46）。每个免疫RECIST的免疫ORR为60.9%(28/46)。中位反应持续时间为9.6个月(95%置信区间[CI]=5.5-不可估计)。中位无进展生存期为8.1个月(95%CI=5.7-14.0)。45例（97.8%）患者出现治疗相关不良事件（TRAEs）。最常见的≥3级TRAEs(>30%)为中性粒细胞计数减少(50.0%),贫血（32.6％），白细胞计数下降（30.4%）。
结论：QL1604联合紫杉醇-顺铂/卡铂在晚期宫颈癌患者的一线治疗中显示出良好的抗肿瘤活性和可控的安全性。对于有禁忌症或不能耐受贝伐单抗的患者群体，程序性细胞死亡蛋白1抑制剂加化疗可能是一种潜在的治疗选择。这需要在III期验证性研究中进一步验证。试验注册ClinicalTrials.gov标识符：NCT04864782。
方法：这是一个多中心，开放标签，单臂,第二阶段研究。在每个21天周期的第1天，招募未接受过全身化疗的晚期宫颈癌患者，接受QL1604联合紫杉醇和顺铂/卡铂，为期6个周期。其次是QL1604维持治疗。
结果：纳入46例患者，中位随访时间为16.5个月。84.8%的患者患有复发性疾病，13.0%的患者患有IVB期疾病。根据晚期实体瘤（RECIST）v1.1的疗效评估标准，客观缓解率（ORR）为58.7％（27/46）。每个免疫RECIST的免疫ORR为60.9%(28/46)。中位反应持续时间为9.6个月(95%置信区间[CI]=5.5-不可估计)。中位无进展生存期为8.1个月(95%CI=5.7-14.0)。45例（97.8%）患者出现治疗相关不良事件（TRAEs）。最常见的≥3级TRAEs(>30%)为中性粒细胞计数减少(50.0%),贫血（32.6％），白细胞计数下降（30.4%）。
结论：QL1604联合紫杉醇-顺铂/卡铂在晚期宫颈癌患者的一线治疗中显示出良好的抗肿瘤活性和可控的安全性。对于有禁忌症或不能耐受贝伐单抗的患者群体，程序性细胞死亡蛋白1抑制剂加化疗可能是一种潜在的治疗选择。这需要在III期验证性研究中进一步验证。试验注册ClinicalTrials.gov标识符：NCT04864782。
