Innovent Biologics has received approval from China's National Medical Products Administration (NMPA) for its second New Drug Application (NDA) for DOVBLERON® (taletrectinib adipate capsule). This next-generation ROS1 tyrosine kinase inhibitor (TKI) is now approved for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).
The approval is based on positive results from the pivotal Phase 2 TRUST-I trial (NCT04395677), a multicenter, open-label, single-arm trial that evaluated the safety, tolerability, and efficacy of taletrectinib in Chinese patients with advanced ROS1-positive NSCLC. The findings were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology (JCO).
TRUST-I Trial Results
The TRUST-I trial demonstrated that taletrectinib continued to show high and durable overall responses and robust activity against intracranial lesions. In ROS1 TKI-naïve patients (n=106), the confirmed objective response rate (cORR, as assessed by an independent review committee, IRC) and intracranial cORR reached as high as 91% and 88%, respectively. After a median follow-up of 23.5 months in TKI-naïve patients, the median duration of response (IRC-assessed) and median progression-free survival (IRC-assessed) were not reached.
Expert Commentary
Caicun Zhou, M.D., Ph.D., Director of the Department of Oncology at Shanghai East Hospital, Tongji University, commented: "We are glad to see that DOVBLERON® has been approved for ROS1-positive NSCLC across treatment lines at a fast pace. DOVBLERON® demonstrated superior efficacy compared to the first-generation TKIs. These TRUST-I results reinforce taletrectinib's high overall response and prolonged PFS. The efficacy and safety profile of DOVBLERON® offers a more effective first-line treatment option and I look forward to its benefit in the ROS1-positive NSCLC patients in China."
Innovent's Perspective
Dr. Hui Zhou, Senior Vice President of Innovent, stated: "The two NDAs approval of DOVBLERON® is a reflection of its potential best-in-class efficacy to fulfill the urgent need of patients with ROS1-positive NSCLC. We recently just launched the first batch of DOVBLERON® to market, rapidly bringing this precision therapy to NSCLC patients who need novel treatment options. Innovent's robust TKI product pipeline—including RETSEMOV®, PEMAZYRE®, DUPERT® and DOVBLERON®—showcases our leadership and synergistic strengths in precision oncology. We endeavor to advance more innovative medicines to enhance patients' quality of life."
About ROS1-positive NSCLC
Lung cancer continues to have one of the highest global incidences and mortality rates, with NSCLC accounting for about 85% of all cases. In China, it is estimated that approximately 2.6% of patients living with NSCLC are ROS1-positive. In patients with metastatic ROS1-positive NSCLC that progressed following initial treatment, many have tumors spread to their brain (up to 55%) or acquired resistance mutations, including G2032R. Next-generation ROS1 TKIs demonstrated robust intracranial and G2032R activity. In the clinical management of ROS1-positive NSCLC patients, the first-line application of the new generation ROS1 TKIs can bring a prolonged progression-free survival and provide patients with greater survival benefits.
About Taletrectinib
Taletrectinib is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor. It is being evaluated for the treatment of patients with advanced ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study.
Taletrectinib has been granted Orphan Drug Designation by the U.S. FDA for the treatment of patients with ROS1-positive NSCLC and other NSCLC indications, and Breakthrough Therapy Designations by both the U.S. FDA and China's NMPA for the treatment of patients with locally advanced or metastatic ROS1-positive NSCLC. Based on pooled results of the TRUST-I and TRUST-II clinical studies, Nuvation Bio Inc. (NYSE: NUVB) submitted an NDA for taletrectinib to the U.S. FDA for the treatment of patients with advanced ROS1-positive NSCLC (line agnostic, full approval). This NDA was accepted by the U.S. FDA for priority review in December 2024.
In June 2021, Innovent and AnHeart Therapeutics (Hangzhou) Co. Ltd., a Nuvation Bio Inc. company, entered into an exclusive license agreement for the co-development and commercialization of taletrectinib in Greater China, including mainland China, Hong Kong, Macau and Taiwan.
