Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China.
Thoracic Medicine Department I, Hunan Tumor Hospital, Changsha, China.
BMC Med. 2023 Feb 24;21(1):72. doi: 10.1186/s12916-023-02738-5.
Iruplinalkib (WX-0593) is an anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor. Here we reported the single-arm, phase II study (INTELLECT) results of the efficacy and safety of iruplinalkib for ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC) patients.
ALK-positive crizotinib-resistant advanced NSCLC patients aged ≥18 years, with Eastern Cooperative Oncology Group performance status of 0-2 were eligible. Patients received iruplinalkib 180 mg orally once daily for a 21-day cycle with a 7-day lead-in phase at 60 mg orally once daily. The primary endpoint was the independent review committee (IRC)-assessed objective response rate (ORR).
From August 7, 2019, to October 30, 2020, 146 patients were included. As of the data cut-off date on November 30, 2021, the median follow-up time was 18.2 months (95% confidence interval [CI] 16.8-18.8). IRC-assessed ORR and disease control rate (DCR) were 69.9% (95% CI 61.7-77.2%) and 96.6% (95% CI 92.2-98.9%), respectively. Investigator-assessed ORR and DCR were 63.0% (95% CI 54.6-70.8%) and 94.5% (95% CI 89.5-97.6%), respectively. Investigator-assessed median duration of response and progression-free survival (the same as median time to progression) were 13.2 months (95% CI 10.4-17.7) and 14.5 months (95% CI 11.7-20.0), respectively. Corresponding IRC-assessed results were 14.4 months (95% CI 13.1-not evaluable [NE]), 19.8 months (95% CI 14.5-NE), and NE (95% CI 14.5-NE), respectively. Investigator-assessed intracranial ORRs were 46% (41/90, 95% CI 35-56%) in patients with central nervous system metastases and 64% (27/42, 95% CI 48-78%) in patients with measurable intracranial lesions. Overall survival data were immature. Treatment-related adverse events (TRAEs) occurred in 136/146 (93.2%) patients. The most common TRAEs were aspartate aminotransferase increased (63 [43.2%]), alanine aminotransferase increased (54 [37.0%]), and blood creatine phosphokinase increased (51 [34.9%]). Dose interruption, reduction, and discontinuation due to TRAEs occurred in 21 (14.4%), 16 (11.0%), and four (2.7%) patients, respectively.
In this study, iruplinalkib (WX-0593) demonstrated favorable efficacy and manageable safety profiles in patients with ALK-positive crizotinib-resistant advanced NSCLC. Iruplinalkib could be a new treatment option for this patient population.
Center for Drug Evaluation of National Medical Products Administration of China: CTR20190789, registered on April 28, 2019; ClinicalTrials.gov: NCT04641754, registered on November 24, 2020.
Iruplinalkib（WX-0593）是一种间变性淋巴瘤激酶（ALK）/c-ros 原癌基因 1（ROS1）酪氨酸激酶抑制剂。在这里，我们报告了 iruplinalkib 治疗 ALK 阳性克唑替尼耐药晚期非小细胞肺癌（NSCLC）患者的疗效和安全性的单臂、二期研究（INTELLECT）结果。
年龄≥18 岁、东部肿瘤协作组体力状态为 0-2 的 ALK 阳性克唑替尼耐药晚期 NSCLC 患者有资格参加。患者接受 iruplinalkib 180mg 口服，每日一次，21 天为一个周期，在 7 天的导入期内口服 60mg，每日一次。主要终点是独立审查委员会（IRC）评估的客观缓解率（ORR）。
自 2019 年 8 月 7 日至 2020 年 10 月 30 日，共纳入 146 例患者。截至 2021 年 11 月 30 日数据截止日期，中位随访时间为 18.2 个月（95%置信区间 [CI] 16.8-18.8）。IRC 评估的 ORR 和疾病控制率（DCR）分别为 69.9%（95% CI 61.7-77.2%）和 96.6%（95% CI 92.2-98.9%）。研究者评估的 ORR 和 DCR 分别为 63.0%（95% CI 54.6-70.8%）和 94.5%（95% CI 89.5-97.6%）。研究者评估的中位缓解持续时间和无进展生存期（与中位进展时间相同）分别为 13.2 个月（95% CI 10.4-17.7）和 14.5 个月（95% CI 11.7-20.0）。相应的 IRC 评估结果分别为 14.4 个月（95% CI 13.1-NE）、19.8 个月（95% CI 14.5-NE）和 NE（95% CI 14.5-NE）。颅内病变可测量的患者颅内 ORR 为 46%（41/90，95% CI 35-56%），有中枢神经系统转移的患者颅内 ORR 为 64%（27/42，95% CI 48-78%）。总生存数据不成熟。136/146（93.2%）例患者发生治疗相关不良事件（TRAEs）。最常见的 TRAEs 为天冬氨酸转氨酶升高（63[43.2%]）、丙氨酸转氨酶升高（54[37.0%]）和血肌酸磷酸激酶升高（51[34.9%]）。因 TRAEs 中断、减少和停止治疗的患者分别为 21（14.4%）、16（11.0%）和 4（2.7%）。
在这项研究中，Iruplinalkib（WX-0593）在 ALK 阳性克唑替尼耐药晚期 NSCLC 患者中显示出良好的疗效和可管理的安全性。Iruplinalkib 可能成为这一患者群体的新治疗选择。
国家药品监督管理局药品审评中心：CTR20190789，注册于 2019 年 4 月 28 日；ClinicalTrials.gov：NCT04641754，注册于 2020 年 11 月 24 日。
