FDA拒绝批准Summit肺癌药依沃西单抗：总生存期未达统计显著标准
美国食品药品监管局（FDA）已向 Summit Therapeutics 发出完全回应信，拒绝以现有形式批准其肺癌药依沃西单抗（ivonescimab）联合含铂化疗的生物制品许可申请。Summit 于11月15日宣布了这一决定。该申请针对的是既往接受过表皮生长因子受体（EGFR）酪氨酸激酶抑制剂治疗的局部晚期或转移性非小细胞肺癌患者。
FDA 在信中表示，在总生存期没有取得统计学显著改善的情况下，该申请尚未确立充分的有效性证据，仅有无进展生存期的获益不足以支持有利的风险获益评估。支撑这一申请的 HARMONi 三期临床试验达到了无进展生存期这一主要终点，但总生存期的主要分析虽呈积极趋势，未达到统计学显著。
Summit 表示，较长期随访的事后分析显示，西方患者、亚洲患者与全部人群的总生存期获益方向一致，风险比为 0.76。该药安全性可接受，不良事件可控，两个治疗组的停药率相近，治疗相关死亡率低。Summit 主席兼联席首席执行官 Robert Duggan 在声明中表示，对等待更多治疗选择的患者和家庭感到失望。
依沃西单抗是一款 PD-1 与 VEGF 双特异性抗体，2024年5月已在中国获批，但在美国和欧洲尚未获批，美国目前也还没有任何一款 PD-1 与 VEGF 双抗药物获批。Summit 表示将继续推进该药在结直肠癌、尿路上皮癌与肾细胞癌等多个适应症的开发，HARMONi-3、HARMONi-7 等多项三期试验正在进行中。
FDA Declines to Approve Summit's Lung Cancer Drug Ivonescimab Over Overall Survival Data
The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter to Summit Therapeutics, declining to approve the Biologics License Application for its lung cancer drug ivonescimab in combination with platinum-containing chemotherapy in its present form. Summit announced the decision on November 15. The application covered patients with locally advanced or metastatic non-small cell lung cancer who had previously received an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor.
In the letter, the FDA determined that substantial evidence of effectiveness is not established in the absence of a statistically significant improvement in overall survival, and that a progression-free survival benefit alone does not support a positive benefit-risk profile. The HARMONi Phase III trial supporting the application met its primary progression-free survival endpoint, but the primary analysis of overall survival did not reach statistical significance despite a positive trend.
Summit said post-hoc analyses of longer-term follow-up showed a consistent overall survival benefit across Western patients, Asian patients and the full population, with a hazard ratio of 0.76. The drug showed an acceptable safety profile with manageable adverse events, comparable discontinuation rates between the treatment arms and low rates of treatment-related death. Robert Duggan, Summit's chairman and co-chief executive, said in the statement that the company was disappointed for patients and their families awaiting additional treatment options.
Ivonescimab is a PD-1 x VEGF bispecific antibody that was first approved in China in May 2024 but remains unapproved in the United States and Europe, and no PD-1 x VEGF bispecific antibody is currently approved in the U.S. Summit said it will continue developing the drug across multiple other indications, including colorectal cancer, urothelial carcinoma and renal cell carcinoma, with Phase III trials such as HARMONi-3 and HARMONi-7 under way.
来源：Summit Therapeutics
发布：GSM·美国（发布链接）
图片来源：图：美国食品药品监管局（FDA）总部大楼入口。FDA 官方图，公共领域，经 Wikimedia Commons。 / Photo: Entrance of the U.S. Food and Drug Administration headquarters. FDA official photo, public domain, via Wikimedia Commons.
GSM Global · 本篇英文版 English edition of this story
