By Fineline Cube China-based biopharma Zai Lab Ltd (NASDAQ: ZLAB) announced receiving two breakthrough therapy designations (BTDs) from the Center for Drug Evaluation (CDE) for its repotrectinib based on positive Phase I/II TRIDENT-1 study results. The designations cover ROS1 positive metastatic non-small cell lung cancer (NSCLC) patients previously treated with one frontline ROS1 TKI + one frontline chemotherapy (EXP-2 cohort), and those treated with one frontline ROS1 TKI without chemotherapy or immunotherapy (EXP-4 cohort).
Drug Background and Licensing Deal
Repotrectinib, a next-generation ROS1/TRK/ALK tyrosine kinase inhibitor (TKI) developed by Turning Point Therapeutics, was licensed by Zai Lab in July 2020 in a USD 176 million deal. Zai Lab secured exclusive development and commercialization rights in Greater China.
Scientific Rationale and Clinical Potential
ALK/ROS1/NTRK1/2/3 fusions drive various tumors. Repotrectinib targets ROS1, NTRK, and ALK-positive patients, showing potential for both TKI-naive and pre-treated patients. It is in Phase I/II TRIDENT-1 (adults) and Phase I/II CARE (pediatrics) studies, demonstrating antitumor activity and sustained responses.
Global Regulatory Status
Repotrectinib has three US BTDs for ROS1+ metastatic NSCLC without prior TKI, and NTRK fusion+ solid tumors pre-treated with one or two TRK TKIs. It also has four US fast-track designations and orphan drug status since 2017.-Fineline Info & Tech