Repotrecitinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on March 4th, 2024
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Mutation in the ROS1 receptor, a crucial tyrosine kinase, accounts for 2% of all non-small-cell lung cancer cases. Currently, Crizotinib and Entrecitinib are the two ROS1 inhibitors in use. However, resistance to these inhibitors has emerged in half of all cases, and their limited activity within the brain reduces their efficacy in metastatic scenarios. Repotrecitinib, a novel small molecule ROS1 antagonist, represents a next-generation option capable of penetrating the brain easily and overcoming steric hindrance—a common resistance mechanism. A recent study has published its findings on the efficacy of Repotrecitinib in treating ROS1 fusion-positive non-small-cell lung cancer.
The combined phase 1 and 2 clinical trial enrolled patients diagnosed with ROS1 fusion-positive non-small-cell lung cancer. Phase 1 involved 103 patients, evaluating the safety and effectiveness of two dosing regimens of Repotrecitinib - 160 mg vs 240 mg. Phase 2 included a cohort of 426 patients, with efficacy analysis focused on 127 individuals. Among these, 71 had no prior treatment with any ROS1 inhibitor, while 56 had received at least one such inhibitor. Patients received an oral dose of 160 mg of Repotrecitinib once daily for two weeks, followed by escalation to 160 mg twice daily. Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors standard. The study findings revealed tumor reduction in 79% of treatment-naive patients and a 38% efficacy rate in those previously treated with a ROS1 inhibitor. This discrepancy in efficacy correlated with roughly a twofold difference in progression-free survival duration. Among the 426 patients analyzed in phase 2, dizziness emerged as the most frequently reported side effect, followed by dysgeusia and paresthesia.
The combined phase 1 and 2 clinical trial enrolled patients diagnosed with ROS1 fusion-positive non-small-cell lung cancer. Phase 1 involved 103 patients, evaluating the safety and effectiveness of two dosing regimens of Repotrecitinib - 160 mg vs 240 mg. Phase 2 included a cohort of 426 patients, with efficacy analysis focused on 127 individuals. Among these, 71 had no prior treatment with any ROS1 inhibitor, while 56 had received at least one such inhibitor. Patients received an oral dose of 160 mg of Repotrecitinib once daily for two weeks, followed by escalation to 160 mg twice daily. Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors standard. The study findings revealed tumor reduction in 79% of treatment-naive patients and a 38% efficacy rate in those previously treated with a ROS1 inhibitor. This discrepancy in efficacy correlated with roughly a twofold difference in progression-free survival duration. Among the 426 patients analyzed in phase 2, dizziness emerged as the most frequently reported side effect, followed by dysgeusia and paresthesia.