Nine months after filing their TROP2-directed antibody-drug conjugate Dato-DXd for a lung cancer indication with the FDA, Daiichi Sankyo and AstraZeneca have pulled the submission.The companies' first attempt, submitted in February, was for the use of Dato-DXd (datopotamab deruxtecan) as a treatment for adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy.That filing was based on the TROPION-Lung01 study, in which Dato-DXd showed a statistically significant improvement in progression-free survival (PFS) in NSCLC patients treated with at least one prior therapy when compared with docetaxel, a standard form of chemotherapy for this patient group, coming in at 5.6 months and 3.7 months, respectively.It wasn't a compelling result, with most of the benefit coming in non-squamous NSCLC patients with little impact in the squamous group, which was why Daiichi Sankyo and AZ tried for a narrower indication.

在向FDA提交TROP2指导的抗体-药物偶联物Dato DXd用于肺癌适应症9个月后，第一三共和阿斯利康撤回了提交。该公司于2月提交的第一次尝试是使用Dato DXd（达托帕单抗deruxtecan）治疗先前接受过全身治疗的局部晚期或转移性非鳞状非小细胞肺癌（NSCLC）成年患者。该文件基于TROPION-Lung01研究，其中Dato DXd显示，与多西他赛（该患者的标准化疗形式）相比，至少接受过一次治疗的NSCLC患者的无进展生存期（PFS）有统计学显着改善组，分别为5.6个月和3.7个月。这并不是一个令人信服的结果，大多数益处来自非鳞状NSCLC患者，而鳞状组的影响很小，这就是为什么Daiichi Sankyo和AZ试图缩小适应症的原因。

Meanwhile, a trend to an improvement in overall survival (OS) in the non-squamous patients failed to become statistically significant.In the intervening months, it has become clear that the FDA was not minded to approve the drug based on that data – even though treatment options for NSCLC remain limited once first-line cancer immunotherapies and drugs targeted at specific mutations have failed.Acknowledging that, the two partners have opted to withdraw the application and refile Dato-DXd based on the mid-stage TROPION-Lung05 trial, still ongoing, which is looking at the use of the ADC in a heavily pretreated group of EGFR-mutated NSCLC patients.That would be a smaller indication, as EGFR mutations occur in around 10% to 15% of NSCLC cases in the US and Europe, and 30% to 40% in Asia.TROPION-.

同时，非鳞状细胞癌患者总生存率（OS）改善的趋势没有统计学意义。在接下来的几个月里，很明显，FDA不打算根据这些数据批准该药物-即使一旦一线癌症免疫疗法和针对特定突变的药物失败，NSCLC的治疗选择仍然有限。承认这一点，两位合作伙伴选择撤回申请，并根据仍在进行的中期TROPION-Lung05试验重新填写Dato DXd，该试验正在研究ADC在经过严重预处理的EGFR突变NSCLC患者中的应用。这将是一个较小的迹象，因为EGFR突变发生在美国和欧洲约10%至15%的NSCLC病例中，而在亚洲约为30%至40%。方向-。