一项联合 NLG207（一种纳米喜树碱）和恩扎卢胺治疗恩扎卢胺治疗后晚期转移性去势抵抗性前列腺癌的单臂 II 期研究
A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin, with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide.
机构信息
Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
出版信息
Oncologist. 2022 Sep 2;27(9):718-e694. doi: 10.1093/oncolo/oyac100.
BACKGROUND
Despite the clinical efficacy of enzalutamide monotherapy in patients with advanced prostate cancer, therapeutic resistance and disease progression are inevitable. We proposed a study to evaluate NLG207, a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor camptothecin, in combination with enzalutamide, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on enzalutamide.
METHODS
This was a single-arm, optimal two-stage, phase II study to evaluate the efficacy of NLG207 in combination with enzalutamide in patients with mCRPC who received prior enzalutamide. A lead-in dose escalation evaluated the recommended phase 2 dose of NLG207 in combination with enzalutamide. Patients received NLG207 via IV infusion every 2 weeks and enzalutamide 160 mg orally once daily.
RESULTS
Between March 2019 and June 2021, four patients were accrued to the lead-in dose escalation. Two of the four patients were evaluable and both experienced DLTs at the NLG207 12 mg/m2 dose level; one DLT was related to a dose delay for noninfective cystitis and myelosuppression, the other a grade 3 noninfective cystitis. Further evaluation of NLG207 in combination with enzalutamide was halted and the study was ultimately terminated. PSA declines from baseline were observed in two patients.
CONCLUSION
NLG207 12 mg/m2 in combination with enzalutamide was not well tolerated in patients with mCRPC following several lines of the standard of care therapy.
CLINICALTRIALS.GOV IDENTIFIER: NCT03531827.
背景
尽管恩扎卢胺单药治疗晚期前列腺癌具有临床疗效，但治疗耐药和疾病进展是不可避免的。我们提出了一项研究，评估 NLG207，一种拓扑异构酶 I 抑制剂喜树碱的纳米药物偶联物（NDC），在恩扎卢胺治疗后进展的转移性去势抵抗性前列腺癌（mCRPC）患者中与恩扎卢胺联合使用的效果。
方法
这是一项单臂、最佳两阶段、二期研究，旨在评估 NLG207 联合恩扎卢胺在接受过恩扎卢胺治疗的 mCRPC 患者中的疗效。一个先导剂量递增评估了 NLG207 联合恩扎卢胺的推荐 2 期剂量。患者每 2 周接受一次 NLG207 静脉输注，每日口服恩扎卢胺 160mg。
结果
在 2019 年 3 月至 2021 年 6 月期间，有 4 名患者入组了先导剂量递增。其中 4 名患者中有 2 名可评估，且均在 NLG207 12mg/m2 剂量水平发生 DLT；1 例 DLT 与非感染性膀胱炎和骨髓抑制的剂量延迟有关，另 1 例为 3 级非感染性膀胱炎。进一步评估 NLG207 联合恩扎卢胺被停止，研究最终终止。两名患者从基线开始 PSA 下降。
结论
在接受过几种标准治疗方案的 mCRPC 患者中，NLG207 12mg/m2 联合恩扎卢胺的耐受性不佳。
临床试验.gov 标识符：NCT03531827。
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