Hubertus-Wald University Cancer Center, Dept. of Medicine II, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
Oncology Institute of Southern Switzerland, Ospedale Regionale Bellinzona e Valli, 6500 Bellinzona, Switzerland.
Eur J Cancer. 2016 Aug;63:55-63. doi: 10.1016/j.ejca.2016.05.003. Epub 2016 Jun 7.
A phase I open-label dose-escalation study was conducted to define the safety, tolerability, and pharmacokinetics (PK) of PankoMab-GEX, a glyco-optimised humanised IgG1, with high affinity to a novel tumour-specific glycopeptide epitope of MUC1 (TA-MUC1) with excellent preclinical anti-tumour activity.
Seventy-four patients with advanced TA-MUC1-positive carcinomas received PankoMab-GEX intravenously every 3 (Q3W), 2 (Q2W), or 1 (QW) week in doses of 1-2200 mg in a three-plus-three dose-escalation design until disease progression (NCT01222624).
No maximum tolerated dose was reached. Adverse events were mainly mild-to-moderate infusion-related reactions (IRRs) by the first infusion in 45% of patients. Only one dose-limiting toxicity, a grade III IRR, was observed. PankoMab-GEX exhibited linear PK over all doses. Mean terminal half-life was 189 ± 66 h (Q3W), without dose dependency. A target trough level ≥50 μg/mL was reached after one infusion with doses ≥1700 mg Q3W in 80% of patients. Clinical benefit in 60 evaluable patients included one complete response in a patient with ovarian cancer treated 483 d and confirmed disease stabilisation in 19 patients lasting a median (range) of 23 (10-109) weeks. All but two of the patients with clinical benefit had received a compounded total dose ≥700 mg over a 3-week period, including 8 of 12 (67%) patients with ovarian cancer.
PankoMab-GEX is safe, well tolerated, and showed promising anti-tumour activity in advanced disease. A phase IIb study is ongoing evaluating the efficacy of PankoMab-GEX as a maintenance therapy in advanced ovarian cancer.
一项 I 期开放标签剂量递增研究旨在确定 PankoMab-GEX 的安全性、耐受性和药代动力学（PK），PankoMab-GEX 是一种具有高亲和力的新型肿瘤特异性糖肽表位 TA-MUC1 的糖优化人源化 IgG1，具有出色的临床前抗肿瘤活性。
74 名晚期 TA-MUC1 阳性癌患者接受静脉内 PankoMab-GEX 治疗，每 3（Q3W）、2（Q2W）或 1（QW）周一次，剂量为 1-2200mg，采用三加三剂量递增设计，直至疾病进展（NCT01222624）。
未达到最大耐受剂量。不良事件主要是前 45%的患者首次输注时出现的轻度至中度输注相关反应（IRR）。仅观察到 1 例剂量限制性毒性，即 3 级 IRR。PankoMab-GEX 在所有剂量下均表现出线性 PK。平均终末半衰期为 189±66h（Q3W），与剂量无关。在接受 Q3W 剂量≥1700mg 的患者中，80%的患者在单次输注后达到目标谷浓度≥50μg/mL。60 名可评估患者的临床获益包括一名卵巢癌患者的完全缓解，该患者接受治疗 483d，19 名患者的疾病稳定持续中位数（范围）为 23（10-109）周。所有具有临床获益的患者除 2 人外，在 3 周内接受的总剂量均超过 700mg，包括 12 名卵巢癌患者中的 8 名（67%）。
PankoMab-GEX 安全、耐受性良好，在晚期疾病中显示出有希望的抗肿瘤活性。一项正在进行的 IIb 期研究评估了 PankoMab-GEX 作为晚期卵巢癌维持治疗的疗效。
