AZD-5335

摘要：在 2025 年柏林欧洲肿瘤内科学会（ESMO）大会上，英国制药巨头阿斯利康公布了其自主研发的新型抗体偶联药物（ADC）AZD5335 的早期临床数据。该药物针对叶酸受体 α 阳性的铂耐药卵巢癌，展现出优异的疗效与可控的安全性，印证了公司深耕内部 ADC 管线的战略正确性，为其在竞争激烈的下一代 ADC 市场中抢占先机奠定基础。自研管线终迎突破 早期数据表现优异 阿斯利康此前凭借与第一三共合作的两款重磅 ADC 药物 Enhertu 和今年初获批的 Datroway 站稳脚跟。如今，公司转向自主研发的战略迎来关键验证。在 ESMO 大会上披露的 I/IIa 期临床试验数据显示，针对 189 名铂耐药卵巢癌患者，AZD5335 在 1.6-2.4mg/kg 剂量范围内均体现出治疗效果。 中位随访 7.8 个月时，该剂量区间内 56.2% 的患者病情未出现恶化。不同剂量组的客观缓解率同样亮眼，1.6mg/kg 组达 56%，2mg/kg 组为 56.1%，2.4mg/kg 组则为 49.2%。阿斯利康早期肿瘤研发副总裁马特・赫尔曼对这一数据给予高度评价，称其充分验证了公司自主 ADC 平台的可靠性。技术优势构筑壁垒 安全性获认可 这款新药的核心竞争力源于阿斯利康自主研发的连接子和拓扑异构酶 I 载荷技术。赫尔曼强调，稳定的连接子 - 载荷系统是未来 ADC 产品组合的核心，公司从过往合作项目中汲取经验，长期投入打造专有 ADC 管线，目标是用 ADC 药物取代传统化疗。 安全性方面，该药物表现出良好的耐受性。最常见的治疗相关不良反应为中性粒细胞减少，2.4mg/kg 剂量组中 3 级及以上病例占 45.9%。值得注意的是，1.6mg/kg 和 2mg/kg 剂量组未出现重大毒性反应，且所有不良反应均与载荷相关，无意外脱靶毒性，符合预期。直面市场竞争 自主布局彰显信心 当前 ADC 领域竞争白热化，众多企业通过并购或授权合作切入赛道。但赫尔曼对公司的市场地位充满信心，他表示阿斯利康是少数自主构建 ADC 技术平台和表面标志物库的企业，能够灵活匹配靶点与有效载荷，持续推进创新。 此次 AZD5335 的临床数据发布，标志着阿斯利康在 ADC 自主研发道路上迈出关键一步。随着内部 7 款覆盖实体瘤和血液系统恶性肿瘤的 ADC 药物逐步推进，这家制药巨头正以技术为矛，在下一代肿瘤疗法的争夺战中开辟属于自己的疆土。 参考来源：https://www.fiercebiotech.com/biotech/esmo-astrazeneca-believes-latest-data-validate-betting-house-adc-pipeline 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

AstraZeneca developed the Duo-O regimen hoping Imfinzi could help Lynparza reach a broader population of patients with ovarian cancer. More than two years after a positive top-line readout, AstraZeneca has to face the reality that a lack of an overall survival (OS) showing for its combo of Imfinzi and Lynparza could prohibit a broader FDA approval in ovarian cancer.At the final analysis of the phase 3 Duo-O trial, AZ’s addition of Imfinzi and Merck & Co.-partnered Lynparza to chemotherapy and bevacizumab failed to prove it can extend lives in newly diagnosed patients with advanced ovarian cancer without tumor BRCA mutations, according to results presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin.The proposed regimen would add Imfinzi to chemo and bevacizumab during induction and then add Imfinzi and Lynparza to bevacizumab during the maintenance phase of treatment. With a median follow-up of about 56 months, the new combo numerically reduced the risk of death versus chemo-bevacizumab by 8%, which didn’t meet the statistical significance bar.The regimen’s poor OS result comes in stark contrast to its 38% improvement in progression-free survival (PFS), the trial's primary endpoint.A separate trial arm testing Imfinzi—but without Lynparza—performed worse than the combo, with a nonsignificant 3% OS advantage and a 16% improvement on PFS.AZ designed the trial hoping Imfinzi could help Lynparza reach a broader population of patients with ovarian cancer. Lynparza is only approved for the first-line maintenance treatment of ovarian cancer, either by itself in BRCA-mutated disease or with bevacizumab in homologous recombination deficiency (HRD)-positive disease. BRCA mutations are a major type of HRD.When Duo-O initially reported positive results on its primary endpoint, PFS, for the Lynparza-Imfinzi combo in 2023, AZ said it would need longer-term data to convince the FDA. An OS benefit is important for this setting, Susan Galbraith, Ph.D., AZ’s head of oncology R&D, said in an interview with Fierce Pharma. The lack of it “represents a challenge from a regulatory perspective, in this context, given the other choices that patients have at this point,” she said.Getting into the other half of the ovarian cancer field marked by HRD-negative tumors has proven challenging for PARP inhibitors like Lynparza.In June, the FDA limited the previously all-inclusive first-line maintenance ovarian cancer label for GSK’s Zejula to only cover HRD-positive disease. The agency made the decision after receiving the final OS analysis of the phase 3 Prima trial. While the study originally supported a broad label for Zejula, the FDA’s analysis suggested a potential trend toward harm in OS in the HRD-negative/not determined subgroup. Combined with a very small PFS improvement, plus several long-term toxicities, the FDA determined that the overall risk-benefit analysis for Zejula was not favorable in the HRD-negative population. In the Duo-O trial, the Imfinzi-Lynparza arm’s performance was slightly better in the non-BRCA HRD-positive subgroup, with a nonsignificant 20% improvement on OS and 51% advantage on PFS. But, as Galbraith noted, these are only hypothesis-generating analyses that don’t confirm efficacy.Still, the subgroup takeaways may give AZ a chance to “think about opportunities for other agents within the portfolio in these different settings,” she said.In AZ’s pipeline, there’s a folate receptor α (FRα)-targeted antibody-drug conjugate, coded AZD5335, that the British pharma is developing for ovarian cancer. The company reported first-in-human data for the agent Saturday at ESMO.