(Lung Cancer) What Is the Efficacy of Next-Generation TKI Inhibitor Repotrectinib?
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- August 13, 2019
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At ASCO 2019 (May 31–June 4) in Chicago, Byoung-Chul Cho presented the efficacy and safety results of repotrectinib (a next-generation ROS1/TRK/ALK tyrosine kinase inhibitor) monotherapy in ROS1 fusion-positive non-small cell lung cancer (NSCLC) patients from the TRIDENT-1 Phase 1 trial.
Trial Design
This Phase 1 trial enrolled both TKI-naive and TKI-pretreated ROS1/TRK/ALK mutation-positive NSCLC patients receiving repotrectinib monotherapy. Primary endpoint: Safety.
Background: ROS1 fusion gene mutations account for 1–2% of NSCLC patients. The only currently available targeted therapy is crizotinib. Repotrectinib, a next-generation ROS1/TRK/ALK TKI, demonstrates ROS1 inhibition potency up to 90-fold greater than crizotinib. In preclinical studies, repotrectinib showed potent kinase inhibition against ROS1 solvent-front mutations (G2032R) and other ROS1 fusion-positive resistance mutations.
Efficacy Results
TKI-naive ROS1 fusion-positive NSCLC patients:
- ORR: 82% (N=9/11)
- Duration of response: Not reached
- Intracranial response: 100% (N=3/3)
TKI-pretreated ROS1 fusion-positive NSCLC patients:
- ORR: 39% (N=7/18)
- ROS1 G2032R mutation subgroup ORR: 40% (N=2/5)
Safety Profile
Adverse event rates:
- Dizziness: 56.6%
- Dysgeusia: 50.6%
- Dyspnea: 30.1%
- Fatigue: 30.1%
- Constipation: 28.9%
- Paresthesia: 28.9%
- Anemia: 27.7%
- Nausea: 22.9%
- Cough: 20.5%
4 patients experienced dose-limiting toxicities: dizziness (3 patients), dyspnea (1 patient), hypoxia (1 patient).
Conclusions
Based on the TRIDENT-1 trial results, Byoung-Chul Cho concluded that repotrectinib monotherapy in ROS1 fusion-positive NSCLC patients achieved ORRs of 39–82%, and adverse events were manageable.
Source: Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1 fusion-positive non-small cell lung cancer (TRIDENT-1 study). 2019 ASCO Annual Meeting, Abstract No: 9011.
Tags: #LungCancer
- Clinical trial drug
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