Jia Jingquan, Moyer Ashley, Lowe Melissa, Bolch Emily, Kortmansky Jeremy, Cho May, Lenz Heinz-Josef, Kalyan Aparna, Niedzwiecki Donna, Strickler John H
Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Pathology, Duke University, Durham, NC, USA.
J Gastrointest Cancer. 2024 Dec 9;56(1):29. doi: 10.1007/s12029-024-01156-x.
MET amplification (amp) is a driver of acquired resistance to epidermal growth factor receptor (EGFR) antibodies in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). Savolitinib is an oral small molecule tyrosine kinase inhibitor that has demonstrated anti-tumor activity in MET-driven advanced solid tumors. We report the results of a phase 2 study of savolitinib in patients with mCRC with MET amp detected by circulating cell free (cf)DNA.
Patients with chemotherapy refractory mCRC and MET amp detected by cfDNA were treated with savolitinib until unacceptable toxicity or disease progression. The primary endpoint was objective response rate. Secondary endpoints were clinical activity and safety.
Five patients were enrolled and treated. Best overall response was stable disease (SD) in two patients, progressive disease (PD) in two patients, and one patient unevaluable for response. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2. The most common TEAEs included fatigue (n = 3) and nausea (n = 3). There were no grade 4 or 5 TEAEs.
Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.
Clinicaltrials.gov Identifier: NCT03592641. Registered on July 17, 2018.
MET扩增是RAS野生型（WT）转移性结直肠癌（mCRC）患者对表皮生长因子受体（EGFR）抗体获得性耐药的驱动因素。赛沃替尼是一种口服小分子酪氨酸激酶抑制剂，已在MET驱动的晚期实体瘤中显示出抗肿瘤活性。我们报告了一项关于赛沃替尼在通过循环游离（cf）DNA检测到MET扩增的mCRC患者中的2期研究结果。
对化疗难治性mCRC且通过cfDNA检测到MET扩增的患者使用赛沃替尼治疗，直至出现不可接受的毒性或疾病进展。主要终点是客观缓解率。次要终点是临床活性和安全性。
五名患者入组并接受治疗。最佳总体反应为两名患者疾病稳定（SD），两名患者疾病进展（PD），一名患者反应不可评估。大多数治疗期间出现的不良事件（TEAE）为1级或2级。最常见的TEAE包括疲劳（n = 3）和恶心（n = 3）。没有4级或5级TEAE。
赛沃替尼耐受性良好；然而，在这一小群经过生物标志物选择的患者中，我们未观察到抗肿瘤活性的证据。
Clinicaltrials.gov标识符：NCT03592641。于2018年7月17日注册。
