Innovent's Taletrectinib (DOVBLERON®) Receives Expanded Approval in China for ROS1-Positive NSCLC
核心洞察
China's NMPA has approved Innovent (搜索)'s taletrectinib for adults with locally advanced or metastatic ROS1 (搜索)-positive non-small cell lung cancer (NSCLC (搜索)).
The approval was based on positive outcomes from the Phase II TRUST-I trial, which showed high and durable overall responses.
In TKI-naïve patients, taletrectinib achieved a confirmed objective response rate of 91% and intracranial cORR of 88%.
Innovent (搜索) Biologics has received approval from China's National Medical Products Administration (NMPA) for its second New Drug Application (NDA) for DOVBLERON® (搜索) (taletrectinib adipate capsule). This next-generation ROS1 (搜索) 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 (搜索)).
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 (搜索). 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 (搜索) 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® (搜索) has been approved for ROS1-positive NSCLC (搜索) 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 (搜索), stated: "The two NDAs approval of DOVBLERON® (搜索) is a reflection of its potential best-in-class efficacy to fulfill the urgent need of patients with ROS1-positive NSCLC (搜索). We recently just launched the first batch of DOVBLERON® to market, rapidly bringing this precision therapy to NSCLC (搜索) 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 (搜索) accounting for about 85% of all cases. In China, it is estimated that approximately 2.6% of patients living with NSCLC are ROS1 (搜索)-positive. In patients with metastatic ROS1-positive NSCLC (搜索) 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 (搜索) inhibitor. It is being evaluated for the treatment of patients with advanced ROS1-positive NSCLC (搜索) 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 (搜索) and other NSCLC (搜索) 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 (搜索) 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.