Taletrectinib

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Clinical Data

Phase I clinical trials for taletrectinib have been completed and further clinical development is ongoing, focusing on both, NTRK and ROS gene fusions. The pharmacokinetics of once-daily, oral administration show that steady-state peak concentration (C max) and exposure (AUC0-8) increased dose dependently from 50-mg to 800-mg doses. Dose-limiting toxicities (grade 3 transaminases increase) occurred in two patients (1,200-mg once-daily dose) and the Maximum Tolerated Dose (MTD) was 800 mg once daily. Most common treatment-related adverse events were nausea (47.8%), diarrhea (43.5%), and vomiting (32.6%), while pain score reductions were observed in the 800-mg once-daily dose cohort. In terms of efficacy, one patient with TPM3-NTRK1 differentiated thyroid cancer achieved a confirmed partial response of 27 months at data cut-off [2].

References

1. Katayama R, Gong B, Togashi N et al. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun. 2019;10(1):3604. 
2. Papadopoulos KP, Borazanci E, Shaw AT, et al. U.S. Phase I First-in-human Study of Taletrectinib (DS-6051b/AB-106), a ROS1/TRK Inhibitor, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2020 Sep 15;26(18):4785-4794.