Zai Lab Announces Breakthrough Therapy Designation 

Zai Lab Limited recently announced the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) granted Breakthrough Therapy Designation for investigational repotrectinib for the treatment of patients with ROS1-positive metastatic non-small-cell lung cancer (NSCLC) who have not been treated with a ROS1 tyrosine kinase inhibitor (TKI). The breakthrough therapy designation for repotrectinib was supported by the initial data from both global and Chinese TKI-naïve ROS1-positive NSCLC patients enrolled in the Phase 1/2 TRIDENT-1 study.

“In granting Breakthrough Therapy Designation, we are pleased to see that the CDE recognizes the promise of repotrectinib,” said Alan Sandler, MD, President and Head of Global Development, Oncology, at Zai Lab. “We believe repotrectinib has the potential to be the best-in-class treatment for patients with ROS1-positive NSCLC, including patients who are either TKI-naïve or TKI-pretreated. We look forward to working 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 the Breakthrough Therapy Designation receive priority communications and guidance from the CDE to promote and expedite the drug development progress.

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 deaths. 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.

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 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.

The US FDA has granted repotrectinib breakthrough therapy designation both for the indication described above as well as for the treatment of patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK tyrosine kinase inhibitors, with or without prior chemotherapy, and have no satisfactory alternative treatments. 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 to develop and commercialize repotrectinib in Greater China.

Zai Lab Limited is a patient-focused, innovative, commercial-stage, global biopharmaceutical company focused on developing and commercializing therapies that address medical conditions with unmet needs in oncology, autoimmune disorders, infectious diseases, and neuroscience. To that end, our experienced team has secured partnerships with leading global biopharmaceutical companies in order to generate a broad pipeline of innovative marketed products and product candidates. We have also built an in-house team with strong product discovery and translational research capabilities and are establishing a pipeline of proprietary product candidates with global rights. Our vision is to become a leading global biopharmaceutical company, discovering, developing, manufacturing, and commercializing our portfolio in order to impact human health worldwide. For more information, visit www.twitter.com/ZaiLab_Global.