FDA 批准新的 CTLA-4 抑制剂用于癌症治疗 — Tremelimumab (Imjudo)

StephenW

FDA 批准新的 CTLA-4 抑制剂用于癌症治疗
— Tremelimumab (Imjudo) 与 durvalumab 联合获得晚期肝癌的批准

作者：Ian Ingram，今日 MedPage 总编辑 2022 年 10 月 24 日

FDA 批准了 Tremelimumab（Imjudo），通过计算机渲染一个透明的身体，突出显示了患病的肝脏。

制药商阿斯利康周一宣布， FDA 已批准 CTLA-4免疫检查点抑制剂曲美木单抗（ Imjudo ）作为不可切除的肝细胞癌（ HCC ）一线免疫治疗组合的一部分。

根据新适应症的具体情况，tremelimumab 与 PD-L1 抑制剂 durvalumab (Imfinzi) 以每 4 周 1,500 mg 的剂量作为单次 300 mg 初始剂量给予 - 称为 STRIDE 方案（单次 tremelimumab，定期间隔杜瓦鲁单抗）。

Tremelimumab 成为继 2011 年 ipilimumab (Yervoy) 获得批准后第二个获得该机构批准的抗 CTLA-4 药物。

支持 tremelimumab-durvalumab 获批的数据来自 III 期 HIMALAYA 试验，这是一项国际开放标签试验，随机分配了 1,300 多名尚未接受全身治疗的晚期、不可切除的 HCC 患者。

总生存期 (OS) 从单药索拉非尼 (Nexavar) 的中位 13.8 个月提高到双重免疫治疗的 16.4 个月，这意味着研究期间死亡风险降低了 22% (HR 0.78, 95% CI 0.66- 0.92，P = 0.0035）。 3 年时，tremelimumab-durvalumab 的 OS 率估计为 31%，而索拉非尼为 20%。

纽约市纪念斯隆凯特琳癌症中心的 HIMALAYA 首席研究员 Ghassan Abou-Alfa 医学博士在一份声明中说：“无法切除的肝癌患者需要耐受性良好的治疗，以显着延长总体生存期。” “安全数据显示，联合用药不会增加严重的肝毒性或出血风险，这对于同时患有晚期肝病的肝癌患者来说是重要因素。”

根据今年早些时候在胃肠道癌症研讨会上公布的试验数据，接受曲美木单抗-durvalumab 或索拉​​非尼治疗的患者的中位无进展生存期相似（分别为 3.78 个月和 4.07 个月），而反应率有利于联合治疗（20.1% 和 5.1% ）。

3/4 级不良事件 (AE) 的发生频率相似（联合用药为 50.5%，索拉非尼为 52.4%），但严重的治疗相关 AE 发生率较低（分别为 25.8% 和 36.9%）。

在其批准公告中，阿斯利康警告使用 tremelimumab-durvalumab 存在胚胎-胎儿毒性风险；用于严重和致命的免疫介导的不良事件（皮肤反应、肺炎、结肠炎、肾炎、肝炎、胰腺炎）；以及免疫介导的内分泌疾病，如 1 型糖尿病、甲状腺疾病、垂体炎和肾上腺功能不全。

StephenW

FDA Approves New CTLA-4 Inhibitor for Cancer Treatment
— Tremelimumab (Imjudo), in combination with durvalumab, lands approval in advanced liver cancer

by Ian Ingram, Managing Editor, MedPage Today October 24, 2022

FDA APPROVED tremelimumab (Imjudo) over a computer rendering of a transparent body with a diseased liver highlighted.

The FDA has approved the CTLA-4 immune checkpoint inhibitor tremelimumab (Imjudo) as part of a first-line immunotherapy combination for unresectable hepatocellular cancer (HCC), drugmaker AstraZeneca announced on Monday.

Under the specifics of the new indication, tremelimumab is given as a single 300 mg priming dose along with the PD-L1 inhibitor durvalumab (Imfinzi) at a dose of 1,500 mg every 4 weeks -- dubbed the STRIDE regimen (single tremelimumab, regular interval durvalumab).

Tremelimumab becomes only the second anti-CTLA-4 drug to garner an approval from the agency, following the 2011 approval of ipilimumab (Yervoy).

Data supporting tremelimumab-durvalumab's approval came from the phase III HIMALAYA trial, an international, open-label trial that randomized more than 1,300 patients with advanced, unresectable HCC who had not yet been treated with systemic therapy.

Overall survival (OS) improved from a median 13.8 months with single-agent sorafenib (Nexavar) to 16.4 months with the dual immunotherapy, representing a 22% reduction in the risk for death during the study period (HR 0.78, 95% CI 0.66-0.92, P=0.0035). At 3 years, OS rates were an estimated 31% with tremelimumab-durvalumab versus 20% with sorafenib.

"Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival," said HIMALAYA principal investigator Ghassan Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center in New York City, in a statement. "Safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease."

According to trial data presented at the Gastrointestinal Cancers Symposium earlier this year, median progression-free survival was similar for patients receiving tremelimumab-durvalumab or sorafenib (3.78 vs 4.07 months, respectively), while response rates favored the combination (20.1% vs 5.1%).

Grade 3/4 adverse events (AEs) occurred at a similar frequency (50.5% with the combination and 52.4% with sorafenib), though serious treatment-related AEs were less frequent (25.8% and 36.9%, respectively).

In its approval announcement, AstraZeneca warned of the risks for embryo-fetal toxicity with tremelimumab-durvalumab; for severe and fatal immune-mediated adverse events (skin reactions, pneumonitis, colitis, nephritis, hepatitis, pancreatitis); and for immune-mediated endocrinopathies such as type 1 diabetes, thyroid disorders, hypophysitis, and adrenal insufficiency.

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曲美木单抗-durvalumab ，曲美木单抗CTL4国内还没有上市，买不到。