Purpose: This phase 1b trial evaluated FAP-IL2v, a novel immune-cytokine engineered to minimize CD25-mediated toxicities, in combination with cetuximab, in patients with recurrent, unresectable, or metastatic head and neck squamous cell carcinoma (HNSCC). Patients and Methods: Patients received FAP-IL2v either on a continuous weekly (QW) schedule, or QW for 4 weeks and then every 2 weeks (Q2W). Cetuximab was dosed at QW or Q2W schedules. The primary objectives were to evaluate the safety and tolerability, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity for the combination of FAP-IL2v with cetuximab. Exploratory objectives included pharmacodynamic analyses. Results: A total of 58 patients were enrolled, 19 patients into the dose-escalation, and 39 patients into the expansion part. The MTD of FAP-IL2v was defined as 10 mg (QW/Q2W) in combination with cetuximab (500 mg/m2, Q2W), which was further tested in the expansion part. The most common FAP-IL2v-related adverse events with a grade 3 or 4 severity were hypophosphatemia (19%), lymphopenia (16%), and infusion-related reaction (14%). The pharmacokinetics of FAP-IL2v in combination with cetuximab was similar to that after administration as monotherapy. Consistent with the proposed mode-of-action, FAP-IL2v preferentially expanded intratumoral NK and CD8 T cells. Four patients achieved a partial response, the objective response rate was 7% (95% CI: 3.2, 14.7). Conclusions: The safety profile of FAP-IL2v in combination with cetuximab was acceptable and pharmacodynamic markers support the proposed mode-of-action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).]

中文翻译：

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免疫细胞因子 Simlukafusp alfa （FAP-IL2v） 联合西妥昔单抗治疗头颈部鳞状细胞癌患者的 1b 期研究


目的：该 1b 期试验评估了 FAP-IL2v，一种新型免疫细胞因子，旨在最大限度地减少 CD25 介导的毒性，与西妥昔单抗联合治疗复发性、不可切除或转移性头颈部鳞状细胞癌 （HNSCC） 患者。患者和方法：患者每周连续 （QW） 接受 FAP-IL2v，或连续 4 周的 QW，然后每 2 周 （Q2W） 接受。西妥昔单抗按 QW 或 Q2W 时间表给药。主要目的是评估 FAP-IL2v 与西妥昔单抗联合治疗的安全性和耐受性、最大耐受剂量 （MTD） 、药代动力学和临床活性。探索性目标包括药效学分析。结果： 共入组 58 例患者，19 例患者进入剂量递增，39 例患者进入扩展部分。FAP-IL2v 的 MTD 定义为 10 mg （QW/Q2W） 与西妥昔单抗 （500 mg/m2，Q2W） 联合使用，在扩增部分进一步测试。最常见的 3 级或 4 级严重程度的 FAP-IL2v 相关不良事件是低磷血症 （19%） 、淋巴细胞减少 （16%） 和输液相关反应 （14%）。FAP-IL2v 联合西妥昔单抗的药代动力学与单药治疗后相似。与所提出的作用方式一致，FAP-IL2v 优先扩增瘤内 NK 和 CD8 T 细胞。4 例患者达到部分缓解，客观缓解率为 7% （95% CI： 3.2， 14.7）。结论： FAP-IL2v 联合西妥昔单抗的安全性是可以接受的，药效学标志物支持这种联合用药的拟议作用方式，但总体低抗肿瘤活性不值得在 HNSCC 中进一步临床探索。[研究BP29842 （NCT02627274） 的 C 部分。