Exposure-Response Analysis of Repotrectinib to Support the Dose Recommendation for Patients With ROS1-Positive NSCLC...

Area of Science:

• Pharmacology and Clinical Trials
• Oncology
• Drug Development

Background:

• Repotrectinib is being evaluated for ROS1-positive NSCLC and NTRK-positive solid tumors.
• Benefit-risk assessment and dose justification are crucial for optimal treatment outcomes.

Purpose of the Study:

• To conduct exposure-response analyses for repotrectinib.
• To support dose justification and benefit-risk assessment for repotrectinib in specific cancer types.

Main Methods:

• Utilized data from the TRIDENT-1 trial, analyzing efficacy (ORR, PFS) and safety endpoints.
• Employed logistic regression and Cox proportional-hazards models to assess exposure-response relationships.
• Compared predicted efficacy and safety for different dosing regimens (160 mg QD/BID vs. 160 mg QD) and food conditions.

Main Results:

• The 160 mg QD/BID regimen showed improved ORR and PFS compared to 160 mg QD for both ROS1-positive NSCLC and NTRK-positive solid tumors.
• Adverse events increased minimally with the recommended dosing regimen.
• Efficacy and safety were consistent across different food intake conditions, supporting administration regardless of food.

Conclusions:

• The 160 mg QD/BID dose of repotrectinib is recommended, demonstrating a favorable efficacy and safety profile.
• Exposure-response analyses provide a robust framework for supporting dosing strategies, especially with dose adjustments.
• Findings support repotrectinib administration irrespective of food intake, enhancing treatment flexibility.