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|Authors||Wei Li, Nong Yang, HuiWen Ma, Huijie Fan, Kunyan Li, Huijuan Wu, Qitao Yu, Yongsheng Wang, Xue Meng, Xicheng Wang, Xintian Qin, Ziping Wang, Yunpeng Liu, Min Tao, Wu Zhuang, Yong Fang, Ping Sun, Kaihua Lu, Jingxun Wu, Caicun Zhou|
|Title||The efficacy and safety of taletrectinib in patients with TKI-naïve or crizotinib-pretreated ROS1-positive non–small cell lung cancer (NSCLC).|
|Journal||Journal of Clinical Oncology|
|Date||June 1, 2022|
|Abstract Text||8572. Background: Taletrectinib (AB-106 / DS-6051b) is a next-generation, potent, CNS- penetrant, selective ROS1 tyrosine kinase inhibitor. The ongoing TRUST study (NCT04395677) is a multicenter, open-label, single-arm, Phase 2 study of taletrectinib in Chinese ROS1-positive NSCLC patients who are TKI -naïve or crizotinib-pretreated. Here we present the updated efficacy and safety results of the study. Methods: The eligible ROS1-positive NSCLC patients were enrolled into either TKI-naïve or crizotinib-pretreated cohorts, and treated with taletrectinib 600mg once daily. The study endpoints included overall response rate (ORR), duration of response (DOR), disease control rate (DCR), overall intracranial response rate (IC-ORR), progression-free survival (PFS), and safety profile. Results: As of the data cutoff date of September 7, 2021, 61 of the 86 stage IV patients enrolled in the study have at least three postbaseline tumor assessment of which 40 patients in the TKI-naïve cohort, and 21 patients in the crizotinib-pretreated cohort (50% patients having at least one prior chemotherapy). In the TKI -naïve cohort, the confirmed ORR by investigators per RECIST 1.1 was 90.0%: [95%CI: 76.3%; 97.2%] (36/40); and the DCR was 95% [95%CI: 83.1%; 99.4%] (38/40). In the crizotinib-pretreated cohort, the confirmed ORR by investigators was 47.6% [95%CI: 25.7%; 70.2%] (10/21); and DCR was 76.2%: [52.8%; 91.8%] (16/21). The mDOR and mPFS are not reached yet for both cohorts. Of 6 patients having brain metastasis and measurable target brain lesions at baseline, the intracranial ORR and IC-DCR were 83.3% and 100%, respectively. Of 4 patients with ROS1 G2032R mutation, 3 patients achieved partial response (PR), and 1 patient achieved stable disease (SD). The most common treatment-related adverse events (TRAEs) include diarrhea, nausea, vomiting, transaminase elevation, anemia, neutrophil count decrease, etc. were Grade 1 or 2, and the most common AEs (below 10%) were ALT/AST increased but reversible. Conclusions: Taletrectinib demonstrated meaningful clinical efficacy in both TKI-naïve and crizotinib-pretreated ROS1 positive NSCLC patients. In particular, taletrectinib showed clinical effectiveness in patients with ROS1 secondary G2032 mutations and patients with brain metastasis. Taletrectinib was well tolerated in this patient population. Clinical trial information: NCT04395677.|
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|ROS1 fusion||lung non-small cell carcinoma||predicted - sensitive||Taletrectinib||Phase II||Actionable||In a Phase II trial, Taletrectinib (DS6051b) treatment in non-small cell lung cancer patients with ROS1 fusions resulted in a 90% (36/40) overall response rate (ORR) and 95% disease control rate (DCR) in TKI-naive patients and 47.6% (10/21) ORR and 76.2% DCR in crizotinib-pretreated patients, intracranial ORR of 83.3% (5/6) and DCR of 100% in patients with baseline brain lesions, and partial responses in 3 of 4 patients with secondary ROS1 G2032R mutations (J Clin Oncol 2022 40:16_suppl, 8572; NCT04395677).||detail...|
|ROS1 fusion ROS1 G2032R||lung non-small cell carcinoma||predicted - sensitive||Taletrectinib||Case Reports/Case Series||Actionable||In a Phase II trial, Taletrectinib (DS6051b) treatment resulted in a partial response in 3 patients and stable disease in 1 patient out of 4 patients with non-small cell lung cancer harboring ROS1 fusions with secondary ROS1 G2032R mutations ((J Clin Oncol 2022 40:16_suppl, 8572; NCT04395677).||detail...|