Department of Melanoma Medical Oncology.
Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Melanoma Res. 2020 Dec;30(6):574-579. doi: 10.1097/CMR.0000000000000694.
Uveal melanoma is a rare and aggressive malignancy and up to half of all patients will develop metastatic disease despite the effective treatment of the primary tumor. Insulin-like growth factors I/II play a fundamental role in the cell migration, proliferation, and apoptosis. IMC-A12, a mAb specifically targets insulin-like growth factor type I receptor, has shown promise in preclinical studies. We performed a multicenter phase II study for patients with metastatic uveal melanoma administered IMC-A12 10 mg/kg IV every two weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response (proportion of patients with complete or partial response), and secondary endpoints were disease control rate, progression-free survival, and overall survival. A total of 18 patients enrolled in this study (10 males and eight females) with a median age. Ten patients (55%) had stable disease, seven patients (38%) had progression as best overall response. No partial response or complete response was observed; however, the disease control rate, defined as complete response + partial response + stable disease ≥3 months, was 50%. Median progression-free survival was 3.1 months, and median overall survival was 13.8 months. Adverse events of any grade occurred in 13 patients (72.2%). Treatment-related grade 3 adverse events were rare, and there were no grade 4 or 5 related adverse events. IMC-A12 was very well tolerated, however, showed limited clinical activity in uveal melanoma as a single agent. Due to its low toxicity profile it could be studied in combination with other pathway-specific agents.
葡萄膜黑色素瘤是一种罕见且侵袭性的恶性肿瘤，尽管对原发性肿瘤进行了有效治疗，但仍有多达一半的患者会发展为转移性疾病。胰岛素样生长因子 I/II 在细胞迁移、增殖和凋亡中发挥着重要作用。IMC-A12 是一种针对胰岛素样生长因子 I 型受体的 mAb，在临床前研究中显示出良好的疗效。我们对转移性葡萄膜黑色素瘤患者进行了一项多中心 II 期研究，给予 IMC-A12 10mg/kg，每两周静脉注射一次，直到疾病进展或出现不可接受的毒性。主要终点是客观缓解（完全或部分缓解患者的比例），次要终点是疾病控制率、无进展生存期和总生存期。共有 18 名患者入组本研究（10 名男性和 8 名女性），中位年龄为 60 岁。10 名患者（55%）病情稳定，7 名患者（38%）病情进展，最佳总体反应为部分缓解。未观察到完全缓解或部分缓解，但疾病控制率（完全缓解+部分缓解+稳定疾病≥3 个月）为 50%。无进展生存期的中位数为 3.1 个月，总生存期的中位数为 13.8 个月。13 名患者（72.2%）出现任何级别的不良事件。罕见治疗相关 3 级不良事件，无 4 级或 5 级相关不良事件。IMC-A12 具有良好的耐受性，然而，作为单一药物在葡萄膜黑色素瘤中的临床活性有限。由于其低毒性特征，它可以与其他特定途径的药物联合研究。
