Efficacy of Taletrectinib to treat ROS1-positive non-small cell lung carcinoma.
DOI:
https://doi.org/10.63501/z87b0k37Keywords:
Taletrectinib; ROS1 inhibitor; Non-small cell lung carcinomaAbstract
ROS1 rearrangements represent a rare but clinically significant oncogenic driver in non-small cell lung carcinoma (NSCLC), occurring in approximately 1–2% of cases. While crizotinib and entrectinib are established targeted therapies, limitations such as central nervous system (CNS) progression and acquired resistance underscore the need for next-generation inhibitors. Taletrectinib, a highly selective ROS1 tyrosine kinase inhibitor, has shown promising activity in both TKI-naïve and pretreated patients, including those with CNS metastases and resistance mutations like G2032R. Early-phase clinical trials report encouraging objective response rates with a manageable safety profile, distinguishing taletrectinib as a potential best-in-class therapy. Its favorable pharmacokinetics and brain penetration may address key gaps left by earlier ROS1 inhibitors, particularly for patients with intracranial disease progression. Given the unmet clinical need, taletrectinib represents an important advancement in precision oncology for ROS1-positive NSCLC. Ongoing phase II and III studies will be crucial in validating its efficacy and positioning within treatment algorithms. Integration of taletrectinib into clinical practice has the potential to improve survival outcomes and quality of life in this molecularly defined subset of NSCLC patients.
References
1. World Health Organization. Cancer. (n.d.).
2. Gendarme, S., Bylicki, O., Chouaid, C., & Guisier, F. (2022). ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date. Current Oncology, 29(2), 641–658. https://doi.org/10.3390/curroncol29020057
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218213s001lbl.pdf
4. Boulanger, M. C., Schneider, J. L., & Lin, J. J. (2024). Advances and future directions in ROS1 fusion-positive lung cancer. The Oncologist, 29(11), 943–956. https://doi.org/10.1093/oncolo/oyae205
5. Li, W., Xiong, A., Yang, N., Fan, H., Yu, Q., Zhao, Y., Wang, Y., Meng, X., Wu, J., Wang, Z., Liu, Y., Wang, X., Qin, X., Lu, K., Zhuang, W., Ren, Y., Zhang, X., Yan, B., Lovly, C. M., & Zhou, C. (2024). Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non–Small Cell Lung Cancer: The Phase II TRUST-I Study. Journal of Clinical Oncology, 42(22), 2660–2670. https://doi.org/10.1200/JCO.24.00731
6. Taletrectinib. (n.d.). Https://Go.Drugbank.Com/Drugs/DB18711.
7. Ou, S.-H. I., Fujiwara, Y., Shaw, A. T., Yamamoto, N., Nakagawa, K., Fan, F., Hao, Y., Gao, Y., Jänne, P. A., & Seto, T. (2021). Efficacy of Taletrectinib (AB-106/DS-6051b) in ROS1+ NSCLC: An Updated Pooled Analysis of U.S. and Japan Phase 1 Studies. JTO Clinical and Research Reports, 2(1), 100108. https://doi.org/10.1016/j.jtocrr.2020.100108
8. Li, W., Yang, N., Ma, H., Fan, H., Li, K., Wu, H., Yu, Q., Wang, Y., Meng, X., Wang, X., Qin, X., Wang, Z., Liu, Y., Tao, M., Zhuang, W., Fang, Y., Sun, P., Lu, K., Wu, J., & Zhou, C. (2022). The efficacy and safety of taletrectinib in patients with TKI-naïve or crizotinib-pretreated ROS1-positive non–small cell lung cancer (NSCLC). Journal of Clinical Oncology, 40(16_suppl), 8572–8572. https://doi.org/10.1200/JCO.2022.40.16_suppl.8572
9. Pérol, M., Li, W., Pennell, N. A., Liu, G., Ohe, Y., de Braud, F., Nagasaka, M., Felip, E., Xiong, A., Zhang, Y., Fan, H., Wang, X., Li, S., Lai, R. K., Ran, F., Zhang, X., Chen, W., Bazhenova, L., & Zhou, C. (2025). Taletrectinib in ROS1 + Non–Small Cell Lung Cancer: TRUST. Journal of Clinical Oncology, 43(16), 1920–1929. https://doi.org/10.1200/JCO-25-00275
10. Wu, Y.-L., Yang, J. C.-H., Kim, D.-W., Lu, S., Zhou, J., Seto, T., Yang, J.-J., Yamamoto, N., Ahn, M.-J., Takahashi, T., Yamanaka, T., Kemner, A., Roychowdhury, D., Paolini, J., Usari, T., Wilner, K. D., & Goto, K. (2018). Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology, 36(14), 1405–1411. https://doi.org/10.1200/JCO.2017.75.5587
11. Drilon, A., Chiu, C.-H., Fan, Y., Cho, B. C., Lu, S., Ahn, M.-J., Krebs, M. G., Liu, S. v., John, T., Otterson, G. A., Tan, D. S. W., Patil, T., Dziadziuszko, R., Massarelli, E., Seto, T., Doebele, R. C., Pitcher, B., Kurtsikidze, N., Heinzmann, S., & Siena, S. (2022). Long-Term Efficacy and Safety of Entrectinib in ROS1 Fusion–Positive NSCLC. JTO Clinical and Research Reports, 3(6), 100332. https://doi.org/10.1016/j.jtocrr.2022.100332
12. Kristi Rosa. (2025, August 23). Pooled TRUST-I and TRUST-II Data Affirm Taletrectinib Benefits for Advanced ROS1+ NSCLC [Internet]. OncLive.
13. Nagasaka, M., Ohe, Y., Zhou, C., Choi, C., Yang, N., Liu, G., Felip, E., Pérol, M., Besse, B., Nieva, J., Raez, L., Pennell, N. A., Dimou, A., Marinis, F. de, Ciardiello, F., Seto, T., Hu, Z., Pan, M., Wang, W., … Ou, S.-H. I. (2023). TRUST-II: a global phase II study of taletrectinib in ROS1 -positive non-small-cell lung cancer and other solid tumors. Future Oncology, 19(2), 123–135. https://doi.org/10.2217/fon-2022-1059
14. Drilon, A., Camidge, D. R., Lin, J. J., Kim, S.-W., Solomon, B. J., Dziadziuszko, R., Besse, B., Goto, K., de Langen, A. J., Wolf, J., Lee, K. H., Popat, S., Springfeld, C., Nagasaka, M., Felip, E., Yang, N., Velcheti, V., Lu, S., Kao, S., … Cho, B. C. (2024). Repotrectinib in ROS1 Fusion–Positive Non–Small-Cell Lung Cancer. New England Journal of Medicine, 390(2), 118–131. https://doi.org/10.1056/NEJMoa2302299
15. Boulanger, M. C., Schneider, J. L., & Lin, J. J. (2024). Advances and future directions in ROS1 fusion-positive lung cancer. The Oncologist, 29(11), 943–956. https://doi.org/10.1093/oncolo/oyae205
16. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. (2025, November 6). U.S Food and Drug Administration.
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