A phase II study of the insulin-like growth factor type I receptor inhibitor IMC-A12 in patients with metastatic uveal melanoma.
A phase II study of the insulin-like growth factor type I receptor inhibitor IMC-A12 in patients with metastatic uveal melanoma.
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DOI：
10.1097/cmr.0000000000000694
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发表时间：
2020-12
影响因子：
2.2
通讯作者：
Patel SP
中科院分区：
文献类型：
--
作者：
Mattei J;Ballhausen A;Bassett R;Shephard M;Chattopadhyay C;Hudgens C;Tetzlaff M;Woodman S;Sato T;Patel SP
葡萄膜黑色素瘤是一种罕见的侵袭性恶性肿瘤，尽管原发性肿瘤得到有效治疗，但高达一半的患者会发生转移性疾病。胰岛素样生长因子I/II在细胞迁移、增殖和凋亡中发挥重要作用。IMC-A12是一种特异性靶向胰岛素样生长因子I型受体的mAb，已在临床前研究中显示出前景。我们对患有转移性葡萄膜黑色素瘤的患者进行了多中心II期研究，每两周IV施用IMC-A12 10 mg/kg，直到疾病进展或不可接受的毒性。主要终点是客观缓解（完全或部分缓解的患者比例），次要终点是疾病控制率、无进展生存期和总生存期。本研究共入组18例患者（10例男性和8例女性），中位年龄。10例患者（55%）病情稳定，7例患者（38%）最佳总体缓解为进展。未观察到部分缓解或完全缓解;然而，疾病控制率（定义为完全缓解+部分缓解+病情稳定≥3个月）为50%。中位无进展生存期为3.1个月，中位总生存期为13.8个月。13例患者（72.2%）发生了任何级别的不良事件。治疗相关的3级不良事件很罕见，没有4级或5级相关不良事件。IMC-A12是非常好的耐受性，然而，作为单一药剂在葡萄膜黑色素瘤中显示出有限的临床活性。由于其毒性低，可与其他特定途径的药剂联合研究。
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.