Section of Endocrine and Sarcoma Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Breast Cancer, Endocrine Tumors and Sarcoma, Division of Cancer, Karolinska University Hospital, Stockholm, Sweden.
Cancer Immunol Immunother. 2020 Nov;69(11):2393-2401. doi: 10.1007/s00262-020-02625-5. Epub 2020 Jun 13.
The majority of patients with advanced gastrointestinal stromal tumor (GIST) develop resistance to imatinib, and subsequent treatments have limited efficacy. Ilixadencel (allogeneic inflammatory dendritic cells) is a cell-based immune primer injected intratumorally that previously has been clinically investigated in metastatic renal cell carcinoma and hepatocellular carcinoma.
The trial was a single arm phase I trial assessing safety and efficacy of ilixadencel in subjects with progressing advanced/metastatic GIST despite ongoing treatment with second or later lines of tyrosine kinase inhibitors (TKI). Three patients were progressing while on sunitinib (second line), one on regorafenib (third line), and two on pazopanib (fourth line). TKI treatment was maintained throughout, while two intratumoral injections of ilixadencel (10 × 10 viable and HLA-DR expressing cells per dose) were administered.
No severe adverse events were found to be related to ilixadencel administration. Four patients showed continued tumor progression at 3 months per RECIST 1.1 and Choi criteria. One patient (on third line regorafenib) had stable disease for 9 months and another patient (on second line sunitinib) had stable disease at end of study (12 months) as per RECIST 1.1. These two patients developed a partial response as per Choi criteria with a duration of 3 and 6 months, respectively. The median progression-free survival (PFS) was 4.0 months.
Ilixadencel treatment presented an acceptable safety profile among advanced GIST patients who developed resistance to TKI. Encouraging radiological tumor responses were detected in 33% of treated patients, supporting further investigation. Clinical trial registration www.clinicaltrials.gov ; NCT: 02432846; registration date: February 22, 2016.
大多数晚期胃肠道间质瘤（GIST）患者对伊马替尼产生耐药性，随后的治疗方法疗效有限。Ilixadencel（异体炎症树突状细胞）是一种瘤内注射的细胞免疫启动剂，此前已在转移性肾细胞癌和肝细胞癌的临床研究中进行了研究。
该试验是一项单臂 I 期试验，评估了进展期/转移性 GIST 患者在继续接受二线或三线酪氨酸激酶抑制剂（TKI）治疗的情况下，使用 ilixadencel 的安全性和疗效。有 3 名患者在使用舒尼替尼（二线）、1 名在使用regorafenib（三线）、2 名在使用 pazopanib（四线）治疗时出现进展。在整个治疗过程中继续进行 TKI 治疗，同时给予两次 ilixadencel（每次剂量 10×10 个活细胞和 HLA-DR 表达细胞）瘤内注射。
未发现与 ilixadencel 给药相关的严重不良事件。4 名患者按 RECIST 1.1 和 Choi 标准在 3 个月时继续肿瘤进展。1 名患者（使用三线regorafenib）疾病稳定 9 个月，另 1 名患者（使用二线舒尼替尼）研究结束时（12 个月）疾病稳定。根据 RECIST 1.1，这两名患者出现 Choi 标准部分缓解，持续时间分别为 3 个月和 6 个月。中位无进展生存期（PFS）为 4.0 个月。
在对 TKI 耐药的晚期 GIST 患者中，Ilixadencel 治疗具有可接受的安全性。在 33%的治疗患者中检测到了令人鼓舞的影像学肿瘤反应，支持进一步研究。临床试验注册 www.clinicaltrials.gov；NCT: 02432846；注册日期：2016 年 2 月 22 日。
