The efficacy and safety of taletrectinib in patients with TKI-naïve or crizotinib-pretreated ROS1-positive non–small cell lung cancer (NSCLC).

Abstract

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.