抗瘤治疗失败后用垂榕素治疗不可切除的 IV 期转移性黑色素瘤：一项 II 期、多中心研究。
Treatment of unresectable stage IV metastatic melanoma with aviscumine after anti-neoplastic treatment failure: a phase II, multi-centre study.
机构信息
Dermatologikum Berlin, Berlin, Germany.
Klinik für Dermatologie, Allergologie und Venerologie, Hauttumorzentrum Hannover (HTZH), Hannover, Germany.
出版信息
J Immunother Cancer. 2014 Aug 19;2:27. doi: 10.1186/s40425-014-0027-z. eCollection 2014.
BACKGROUND
Aviscumine, a recombinant plant protein, is an immune modulator that induces ribotoxic stress at the 28S ribosomal RNA subunit. In this way cytokine release and T-cell responses are enhanced. This phase II trial was conducted to test the efficacy and safety of aviscumine in patients with systemically pre-treated metastatic melanoma stage IV.
METHODS
A total of 32 patients with progressive stage IV melanoma after failure of standard therapy were enrolled onto a single-arm, multi-centre, open-label, phase II trial. All patients had an ECOG performance status of 0 or 1. Patients received 350 ng aviscumine twice weekly by subcutaneous injection until progression. The primary end points were progression-free survival (PFS) and overall survival (OS). Safety was assessed as adverse events (AEs). Tumor response was assessed every eight weeks and survival of patients was followed up to one year after the end of therapy. Thirty one patients (intent-to-treat population (ITT)) were assessed for efficacy; safety was assessed in the whole population.
RESULTS
One patient achieved a partial response (PR) and 10 patients showed stable disease/no change (SD). The median progression-free survival (mPFS) was 63 days (95% CI 57-85) and median overall survival (mOS) was 335 days (95% CI 210-604). In total 210 treatment-emergent adverse events were recorded. Grade 1 or 2 AEs occurred in 72% of patients and were mostly application-site effects such as pruritus Grade 3-4 treatment-emergent drug-related adverse events occurred in 9% of patients.
CONCLUSION
These results suggest that aviscumine may have a clinical impact in patients with previously treated metastatic melanoma and provide rationale for further clinical evaluation of this agent. In the light of effective new immune checkpoint blockers it might be a candidate for combinations with these agents.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT00658437.
背景
Aviscumine 是一种重组植物蛋白，作为一种免疫调节剂，它可在 28S 核糖体 RNA 亚基上诱导核糖体毒性应激，从而增强细胞因子释放和 T 细胞反应。这项 II 期试验旨在测试 aviscumine 在系统预处理转移性黑色素瘤 IV 期患者中的疗效和安全性。
方法
共纳入 32 例标准治疗失败后进展为 IV 期黑色素瘤的患者，进行了一项单臂、多中心、开放性、II 期试验。所有患者 ECOG 体能状态评分为 0 或 1。患者接受每周两次皮下注射 350ng aviscumine，直至疾病进展。主要终点是无进展生存期（PFS）和总生存期（OS）。安全性评估为不良事件（AE）。每 8 周评估肿瘤反应，治疗结束后随访患者 1 年。31 例患者（意向治疗人群（ITT））进行疗效评估；所有患者进行安全性评估。
结果
1 例患者达到部分缓解（PR），10 例患者表现为疾病稳定/无进展（SD）。中位无进展生存期（mPFS）为 63 天（95%CI 57-85），中位总生存期（mOS）为 335 天（95%CI 210-604）。共记录了 210 次治疗出现的不良事件。72%的患者出现 1 级或 2 级 AE，主要为瘙痒等局部用药反应；3-4 级治疗出现的药物相关不良事件发生率为 9%。
结论
这些结果表明，aviscumine 可能对既往治疗的转移性黑色素瘤患者有临床影响，并为进一步评估该药物提供了依据。鉴于有效的新型免疫检查点抑制剂，它可能是与这些药物联合应用的候选药物。
试验注册
ClinicalTrials.gov：NCT00658437。
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