Pictured: 3D illustration of antibody-drug conjugate molecules carrying toxic payloads/iStock, Love Employee

图为：携带有毒有效载荷的抗体-药物结合物分子的3D插图/iStock，Love Employee

MacroGenics’ stock dropped by as much as 70% Friday morning after the biotech disclosed five deaths in the Phase II TAMARACK trial for its investigational antibody-drug conjugate vobramitamab duocarmazine in metastatic castration-resistant prostate cancer.

MacroGenics的股价在周五早上下跌了70%，此前该生物技术公司在TAMARACK II期试验中公布了5人死亡，该试验是针对其研究性抗体药物偶联物vobramitamab duocamazine治疗转移性去势抵抗性前列腺癌。

The five fatal adverse events included two grade 5 toxicities—one case of acute myocardial infarction and another of cardiac arrest—which were deemed unrelated to the study treatment.

五种致命不良事件包括两种5级毒性，一种是急性心肌梗死，另一种是心脏骤停，被认为与研究治疗无关。

Two of the deaths were caused by pneumonitis, or inflammation of lung tissues, while the fifth patient died of pleural effusion, or the build-up of fluids in the pleural cavity. MacroGenics is still investigating these three deaths. TAMARACK is ongoing and follow-up is still incomplete.

其中两人死于肺炎或肺组织炎症，而第五名患者死于胸腔积液或胸腔积液。宏基因组学仍在调查这三起死亡事件。塔马拉克正在进行中，后续行动仍不完整。

Despite these fatal toxicities and negative stock reaction, CEO Scott Koenig in an investor call on Thursday struck a positive note, calling the candidate’s side effects “extremely manageable.” Study investigators, he continued, are “very comfortable” with managing these toxicities “and are very encouraged by both the safety and obviously, the activity data they’ve seen.”.

尽管有这些致命的毒性和负面的股票反应，首席执行官斯科特·柯尼格（ScottKoenig）在周四的一次投资者电话会议上发表了积极的评论，称候选人的副作用“极其可控”。他继续说，研究调查人员对管理这些毒性“非常满意”，他们看到的安全性和明显的活动数据都非常鼓舞。”。

Vobramitamab duocarmazine, also called vobra duo, is an investigational antibody-drug conjugate (ADC) therapy designed to target the B7-H3 antigen, which is overexpressed in cancer cells. Vobra duo carries the toxic payload seco-duocarmycin hydroxybenzamide azaindole, an alkylating agent that damages DNA in cancer cells and triggers their cell death, according to MacroGenics’ website..

Vobramitamab duocamazine，也称为vobra duo，是一种研究性抗体-药物偶联物（ADC）疗法，旨在靶向在癌细胞中过表达的B7-H3抗原。据MacroGenics网站报道，Vobra duo携带有毒有效载荷seco duocamycin hydroxybenzamide azaindole，一种烷化剂，可破坏癌细胞中的DNA并引发其细胞死亡。。

The Maryland-based biotech is developing vobra duo as a treatment for various solid tumors, including non-small cell lung cancer, melanoma and squamous cell carcinoma of the head and neck. Its most mature program, however, is in metastatic castration-resistant prostate cancer (mCRPC), for which it is running the mid-stage, open-label TAMARACK study..

总部位于马里兰州的生物技术公司正在开发vobra duo，用于治疗各种实体瘤，包括非小细胞肺癌、黑色素瘤和头颈部鳞状细胞癌。然而，其最成熟的项目是转移性去势抵抗性前列腺癌（mCRPC），目前正在进行中期开放标签塔马拉克研究。。

Data from TAMARACK, which MacroGenics also released on Friday, show that the lower, 2.0-mg/kg dose of vobra duo elicited an overall response rate (ORR) of 24.4%, when counting even unconfirmed instances of treatment response. At the higher, 2.7-mg/kg dose, vobra duo treatment resulted in a 43.8% ORR.

MacroGenics也于周五发布了TAMARACK的数据，数据显示，较低剂量（2.0 mg/kg）的vobra duo在计算未经证实的治疗反应时，总体反应率（ORR）为24.4%。在较高的2.7 mg/kg剂量下，vobra-duo治疗导致43.8%的ORR。

Disease control rates were 91.1% and 87.5% for the low and high rates, respectively..

低发病率和高发病率的疾病控制率分别为91.1%和87.5%。。

With these data in hand, MacroGenics is preparing for a potential Phase III study in mCRPC, slated for 2025. The decision to push through with this late-stage trial will depend on the final analysis of TAMARACK, including progression-free survival data, when available, according to the press release..

有了这些数据，MacroGenics正在为计划于2025年进行的mCRPC潜在的III期研究做准备。根据新闻稿，推进这项晚期试验的决定将取决于塔马拉克的最终分析，包括无进展生存数据（如果可用）。。

MacroGenics has had a history of patient deaths in its trials. In September 2021, the biotech posted Phase I data for vobra duo, revealing two fatal grade 5 toxicities—one with an unknown cause and the other attributable to COVID-19.

MacroGenics在其试验中有患者死亡的历史。2021年9月，生物技术公司发布了vobra duo的第一阶段数据，揭示了两种致命的5级毒性，一种原因不明，另一种归因于COVID-19。

Nearly a year later, in June 2022, MacroGenics reported seven patient deaths, this time in connection with a study of its investigational antibody enoblituzumab, which also targets the B7-H3 antigen, forcing the company to discontinue its Phase II study in head and neck cancer.

近一年后，即2022年6月，MacroGenics报告了7例患者死亡，这一次与其研究抗体enoblituzumab的研究有关，该抗体也针对B7-H3抗原，迫使该公司停止了头颈癌的II期研究。

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

特里斯坦·马纳拉克（TristanManalac）是一位独立的科学作家，总部位于菲律宾马尼拉。在LinkedIn上联系他，或发电子邮件给他tristan@tristanmanalac.com或tristan.manalac@biospace.com.