Akeso announced that its internally developed PD-1/CTLA-4 bispecific antibody, cadonilimab, has received approval from the National Medical Products Administration (NMPA) for a new indication: cadonilimab in combination with fluoropyrimidine and platinum-based chemotherapy for first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

Akeso宣布，其内部开发的PD-1/CTLA-4双特异性抗体cadonilimab已获得美国国家医疗产品管理局（NMPA）的批准，用于一种新的适应症：cadonilimab联合氟嘧啶和铂类化疗，用于局部晚期不可切除或转移性胃或胃食管交界处（G/GEJ）腺癌患者的一线治疗。

This is the second indication approval for cadonilimab in China, following its initial approval for marketing in June 2022. The approval of the new indication for cadonilimab combination therapy for first-line treatment of gastric/GEJ cancer is based on the COMPASSION-15/AK104-302 study. In the COMPASSION-15 study, the proportion of patients with PD-L1 CPS  less than  5 and PD-L1 CPS less than 1 in the Intention-to-Treat (ITT) population reached 49.8% and 23%, respectively, which is significantly higher than the data disclosed in previous phase III studies of other immunotherapies for first-line treatment..

这是继2022年6月首次批准上市后，卡多尼单抗在中国的第二次适应症批准。cadonilimab联合治疗胃癌/GEJ癌一线治疗的新适应症的批准是基于同情-15/AK104-302研究。在CISIC-15研究中，意向治疗（ITT）人群中PD-L1 CPS小于5和PD-L1 CPS小于1的患者比例分别达到49.8%和23%，显着高于之前其他一线免疫疗法III期研究中披露的数据。。

In November 2023, the interim analysis of the study achieved the primary endpoint of overall survival (OS). The results showed that the cadonilimab combination therapy significantly reduced the risk of death in advanced gastric cancer patients across all PD-L1 expression levels (including those with PD-L1 CPS  greater than 5 ), extending overall survival benefits and demonstrating notable advantages in objective response and long-term survival.

2023年11月，该研究的中期分析达到了总生存期（OS）的主要终点。结果显示，卡多尼单抗联合治疗显着降低了所有PD-L1表达水平（包括PD-L1 CP大于5的患者）的晚期胃癌患者的死亡风险，延长了总体生存获益，并在客观反应和长期生存方面显示出显着优势。

Previous phase III trials of PD-1 inhibitors combined with chemotherapy showed limited or no clinical benefit for patients with low or negative PD-L1 expression..

先前的PD-1抑制剂联合化疗的III期临床试验显示，对于PD-L1表达低或阴性的患者，临床获益有限或无临床获益。。

The results of the COMPASSION-15 study were presented as an oral report at the 2024 AACR. In the ITT population, the median overall survival (mOS) for the cadonilimab regimen reached 15.0 months, compared to 10.8 months in the control group, extending overall survival by 4.2 months and reducing the risk of death by 38% (HR=0.62).

同情-15研究的结果在2024年AACR上以口头报告的形式呈现。在ITT人群中，卡多尼单抗方案的中位总生存期（mOS）达到15.0个月，而对照组为10.8个月，总生存期延长了4.2个月，死亡风险降低了38%（HR=0.62）。

In the PD-L1 CPS less than 5 group, the mOS for the cadonilimab regimen was 14.8 months, with a 30% reduction in the risk of death compared to the control group (11.1 months, HR=0.70). For the PD-L1 CPS greater han ≥5 group, the mOS had not yet been reached, but the risk of death was reduced by 44% compared to the control group (10.6 months, HR=0.56)..

在PD-L1 CPS小于5组中，卡多尼单抗方案的mOS为14.8个月，与对照组相比，死亡风险降低了30%（11.1个月，HR=0.70）。对于PD-L1 CPS大汉族≥5组，尚未达到mOS，但与对照组相比，死亡风险降低了44%（10.6个月，HR=0.56）。。

COMPASSION-15's principal investigator, Professor Ji Jiafu from Peking University Cancer Hospital, stated: “ The prognosis for advanced gastric cancer is poor. While currently approved immunotherapy options have improved efficacy compared to traditional chemotherapy, there remains significant potential for enhancement.

慈悲15号的首席研究员、北京大学肿瘤医院的季家福教授表示：“进展期胃癌的预后很差。虽然目前批准的免疫治疗方案与传统化疗相比疗效有所提高，但仍有很大的增强潜力。

The cadonilimab combination therapy has substantially increased the objective response rate and overall survival in the general population while reducing disease-related mortality. Remarkably, cadonilimab shows significant overall survival benefits not only in patients with high PD-L1 CPS expression but also in those with low or negative PD-L1 CPS expression..

卡多尼单抗联合治疗大大提高了普通人群的客观缓解率和总生存率，同时降低了与疾病相关的死亡率。值得注意的是，卡多尼单抗不仅在PD-L1 CPS表达高的患者中，而且在PD-L1 CPS表达低或阴性的患者中，显示出显着的总体生存益处。。

The approval of cadonilimab as a first-line treatment effectively addresses the efficacy gap of PD-1/L1 monoclonal antibodies in patients with low or negative PD-L1 expression, providing a more comprehensive and effective immunotherapy option for advanced gastric cancer. This advancement benefits all patient populations and presents new opportunities for the global development of gastric cancer immunotherapy, carrying important clinical implications..

卡多尼单抗作为一线治疗的批准有效地解决了PD-1/L1单克隆抗体在PD-L1表达低或阴性患者中的疗效差距，为晚期胃癌提供了更全面和有效的免疫治疗选择。这一进步使所有患者群体受益，并为胃癌免疫疗法的全球发展提供了新的机会，具有重要的临床意义。。

COMPASSION-15's principal investigator, Professor Shen Lin from Peking University Cancer Hospital, stated: “We are delighted by the successful approval of cadonilimab combination therapy for the first-line treatment of advanced gastric cancer. This regimen offers significant advantages over current immunotherapy options in clinical practice, providing a superior choice not only for patients with high PD-L1 expression but also for those with low or negative PD-L1 expression, who previously lacked effective treatment options.Cadonilimab addresses the limitations of single-target immunotherapy and exemplifies the synergistic mechanism of dual immune therapy with 'anti-PD-1 + anti-CTLA-4,' thereby filling an important clinical gap in the treatment of advanced gastric cancer.

“同情心15号”的首席研究员、北京大学肿瘤医院的沈林教授表示：“我们很高兴卡多尼单抗联合治疗成功批准用于晚期胃癌的一线治疗。该方案在临床实践中比目前的免疫治疗方案具有显着优势，不仅为PD-L1表达高的患者提供了更好的选择，而且为PD-L1表达低或阴性的患者提供了更好的选择，这些患者以前缺乏有效的治疗选择。卡多尼单抗解决了单靶点免疫治疗的局限性，并举例说明了“抗PD-1+抗CTLA-4”双重免疫治疗的协同机制，从而填补了晚期胃癌治疗的重要临床空白。

Beyond first-line approval, the phase III clinical study (AK109-301) of cadonilimab combined with pulocimab (AK109, VEGFR-2) for treating advanced gastric cancer that has progressed after PD-1/L1 inhibitor plus chemotherapy has been initiated. There is currently a lack of effective standard treatments for patients with acquired resistance to immunotherapy, and we eagerly anticipate that this new combination regimen will yield improved results in second-line therapy for these patients, ultimately providing clinicians with more effective tools for cancer treatment.”.

除了一线批准外，卡多尼单抗联合普洛单抗（AK109，VEGFR-2）治疗PD-1/L1抑制剂加化疗后进展的晚期胃癌的III期临床研究（AK109-301）已经开始。目前缺乏针对获得性免疫治疗耐药患者的有效标准治疗方法，我们热切期望这种新的联合治疗方案将在这些患者的二线治疗中产生更好的结果，最终为临床医生提供更有效的癌症治疗工具。“。

Condition: Gastric + Gastroesophageal Junction Cancer

病情：胃+胃食管交界癌

Type: drug

类型：药物