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首页> 外文OA文献 >Phase I study of IMGN901, a CD56-targeting antibody-drug conjugate, in patients with CD56-positive solid tumors.
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Phase I study of IMGN901, a CD56-targeting antibody-drug conjugate, in patients with CD56-positive solid tumors.

机译：I期研究ImGN901，一种CD56靶向抗体 - 药物偶联物，用于CD56阳性实体瘤患者。

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IMGN901 is a CD56-targeting antibody-drug conjugate designed for tumor-selective delivery of the cytotoxic maytansinoid DM1. This phase 1 study investigated the safety, tolerability, pharmacokinetics, and preliminary activity of IMGN901 in patients with CD56-expressing solid tumors. Methods Patients were enrolled in cohorts of escalating IMGN901 doses, administered intravenously, on 3 consecutive days every 21 days. A dose-expansion phase accrued patients with small cell lung cancer (SCLC), Merkel cell carcinoma (MCC), or ovarian cancer. Results Fifty-two patients were treated at doses escalating from 4 to 94 mg/m2/day. The maximum tolerated dose (MTD) was determined to be 75 mg/m2. Dose-limiting toxicities included fatigue, neuropathy, headache or meningitis-like symptoms, chest pain, dyspnea, and myalgias. In the dose-expansion phase (n = 45), seven patients received 75 mg/m2 and 38 received 60 mg/m2 for up to 21 cycles. The recommended phase 2 dose (RP2D) was established at 60 mg/m2 during dose expansion. Overall, treatment-emergent adverse events (TEAEs) were experienced by 96.9 % of all patients, the majority of which were Grade 1 or 2. The most commonly reported Grade 3 or 4 TEAEs were hyponatremia and dyspnea (each 8.2 %). Responses included 1 complete response (CR), 1 clinical CR, and 1 unconfirmed partial response (PR) in MCC; and 1 unconfirmed PR in SCLC. Stable disease was seen for 25 % of all evaluable patients who received doses ≥60 mg/m2. Conclusions The RP2D for IMGN901 of 60 mg/m2 administered for 3 consecutive days every 3 weeks was associated with an acceptable tolerability profile. Objective responses were observed in patients with advanced CD56+ cancers.
机译：IMGN901是靶向CD56的抗体-药物偶联物，设计用于肿瘤选择性递送细胞毒性美登木素生物碱DM1。这项1期研究调查了IMGN901在表达CD56的实体瘤患者中的安全性，耐受性，药代动力学和初步活性。方法患者参加了每21天连续3天静脉注射IMGN901剂量递增的队列。剂量扩大阶段的患者为小细胞肺癌（SCLC），默克尔细胞癌（MCC）或卵巢癌。结果52例患者接受的剂量从4毫克/平方米/天提高到94毫克/平方米/天。最大耐受剂量（MTD）确定为75 mg / m2。剂量限制性毒性包括疲劳，神经病，头痛或脑膜炎样症状，胸痛，呼吸困难和肌痛。在剂量扩大阶段（n = 45），七名患者接受75 mg / m2的治疗，而38名患者接受60 mg / m2的治疗，最多可进行21个周期。在剂量扩展期间，建议的第2阶段剂量（RP2D）确定为60 mg / m2。总体而言，所有患者中96.9％经历了治疗紧急不良事件（TEAE），其中大多数为1级或2级。最常报告的3级或4级TEAE为低钠血症和呼吸困难（每例8.2％）。缓解包括1例完全缓解（CR），1例临床CR和1例未经证实的部分缓解（PR）； 1个SCLC中未经证实的PR。在接受≥60 mg / m2剂量评估的所有可评估患者中，有25％观察到稳定的疾病。结论IMGN901的RP2D每3周连续3天给药60 mg / m2，这与可接受的耐受性有关。在晚期CD56 +癌症患者中观察到客观反应。

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