On June 10, 2022 Zai Lab Limited, a patient-focused, innovative, commercial-stage, global biopharmaceutical company, reported that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) granted two Breakthrough Therapy Designations for investigational repotrectinib for the treatment of patients with ROS1-positive metastatic NSCLC who have received one prior line of ROS1 TKI and one prior line of platinum-based chemotherapy (EXP-2) and for those with ROS1-positive metastatic NSCLC who have received one prior line of ROS1 TKI and no chemotherapy or immunotherapy (EXP-4) (Press release, Zai Laboratory, JUN 10, 2022, View Source [SID1234633496]). The Breakthrough Therapy Designations for repotrectinib were supported by the data from both global and Chinese TKI-pretreated ROS1-positive NSCLC patients enrolled in the Phase 1/2 TRIDENT-1 study.
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"Since repotrectinib received Breakthrough Therapy Designation by the CDE earlier this year for ROS1-positive TKI-naïve patients, today’s recognition further supports repotrectinib as a potential best-in-class treatment for ROS1-positive NSCLC in both TKI-naïve and pretreated patients in China," said Alan Sandler, M.D., President and Head of Global Development, Oncology at Zai Lab. "There remain significant unmet needs for ROS1-positive NSCLC patients, and we look forward to our continued partnership with regulatory authorities in China to bring this important medicine to patients in need as soon as possible."
The Breakthrough Therapy Designation review policy is designed to facilitate the development and expeditious review of novel medicines that are intended for the prevention or treatment of serious, life-threatening diseases or diseases that severely impact the quality of life for which there is no existing treatment, or where sufficient evidence indicates advantages of the novel drug over currently available treatment options. Drugs granted Breakthrough Therapy Designations receive priority communications and guidance from the CDE to promote and expedite the drug development process.
Lung cancer is both the most commonly diagnosed cancer type and the leading cause of cancer death in China. The incidence of lung cancer in China in 2020 was 815,563 cases, with 714,699 deaths1. NSCLC accounts for approximately 85% of lung cancer, and about 70% of NSCLC is locally advanced or metastatic at initial diagnosis. In China, ROS1 rearrangements occur in 2-3% of patients with advanced NSCLC.
1Globocan 2020.
About Repotrectinib
Repotrectinib is a next-generation kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers of NSCLC and advanced solid tumors. Tumors with mutations to their ROS1 and NTRK genes have a higher likelihood of developing resistance to existing targeted therapies. In many cases, these mutations prevent existing medicine from targeting and binding to the tumor as effectively as tumors that do not carry the mutations. Repotrectinib is designed to be smaller and less bulky than existing targeted therapies and may circumvent some of the resistance mechanisms found in tumors with ROS1 and NTRK mutations. Zai Lab and Turning Point Therapeutics, Inc. are studying repotrectinib in TRIDENT-1, a registrational Phase 1/2 study in adults, and CARE, a Phase 1/2 study in pediatric patients. The compound has shown antitumor activity and durable responses among kinase inhibitor treatment-naïve and pre-treated patients. Zai Lab is enrolling patients in the registrational Phase 2 portion of TRIDENT-1 in Greater China, while Turning Point Therapeutics is enrolling patients in other regions of the world.
Repotrectinib has been granted three Breakthrough Therapy Designations from the U.S. Food and Drug Administration in: ROS1-positive metastatic NSCLC patients who have not been treated with a ROS1 TKI; patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK TKIs, with or without prior chemotherapy, and have no satisfactory alternative treatments; and ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and who have not received prior platinum-based chemotherapy. Additionally, repotrectinib was previously granted four Fast-Track designations in: ROS1-positive advanced NSCLC patients who are ROS1 TKI naïve; ROS1-positive advanced NSCLC patients who have been previously treated with one prior line of platinum-based chemotherapy and one prior ROS1 TKI; ROS1-positive advanced NSCLC patients pretreated with one prior ROS1 TKI without prior platinum-based chemotherapy; and NTRK-positive patients with advanced solid tumors who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs and have no satisfactory alternative treatments. Repotrectinib was also granted an Orphan Drug designation in 2017.
Zai Lab has an exclusive license agreement with Turning Point Therapeutics to develop and commercialize repotrectinib in Greater China.