FDA Approves Updated IBTROZI Label With Nearly 50-Month Duration of Response in TKI-Naive ROS1+ NSCLC
核心洞察
The FDA approved a supplemental New Drug Application for taletrectinib (IBTROZI), updating the label with a median duration of response of 49.7 months in TKI-naive ROS1 (搜索)-positive NSCLC.
Updated data from the phase 2 TRUST-I and TRUST-II trials reflect a median follow-up of 51 months in TRUST-I plus 14 additional months of follow-up.
The approval arrived four months ahead of the January 4, 2027 PDUFA date, with no changes to safety labeling and no new safety signals identified.
The FDA has approved a supplemental New Drug Application (sNDA) for taletrectinib (IBTROZI), a ROS1 (搜索) inhibitor, updating the U.S. label for adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (搜索) (NSCLC) to reflect a median duration of response (DOR) of 49.7 months (95% CI, 41.3-not reached [NR]) in TKI-naive patients, according to Nuvation Bio. The approval, announced September 16, 2026, came four months ahead of the original Prescription Drug User Fee Act (PDUFA) date of January 4, 2027.
The updated label incorporates a median follow-up of 51 months for patients in the phase 2 TRUST-I study (NCT04395677) and an additional 14 months of data from both the TRUST-I and TRUST-II (NCT04919811) pivotal studies, as of an August 2025 data cutoff. The company reported that the update came with no changes to the safety sections of labeling and no new safety signals identified with longer follow-up.
"This approval is a significant milestone for IBTROZI because this data is now part of the FDA-approved label, something physicians and patients can turn to directly," said David Hung, M.D., founder, president, and chief executive officer of Nuvation Bio. "A median duration of response of more than four years—the longest median DOR reported for an FDA-approved ROS1 (搜索) TKI—is a remarkable outcome for people living with ROS1+ NSCLC, and having it in the label means something real for patients: a clearer sense of how long they might expect to stay on treatment, and more confidence in what that path could look like at a moment when a new diagnosis can feel overwhelming. It also gives physicians additional evidence to support using IBTROZI early in a patient's care, when that choice matters most."
Efficacy and Follow-Up Data
Beyond the median DOR of 49.7 months, the updated data set reported a median progression-free survival of 49.6 months (95% CI, 34.5-NR) and a median overall survival (OS) that was not reached (95% CI, 41.6-NR). The 3-year OS rate was 65.3%. According to Nuvation Bio, many patients remained on therapy for extended periods with continued response—some for multiple years—highlighting the long-term durability and tolerability of the agent. The data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 and simultaneously published in the Journal of Clinical Oncology.
The TRUST clinical program comprises three registrational studies. TRUST-I and TRUST-II are phase 2 single-arm studies evaluating IBTROZI in adults with advanced ROS1 (搜索)+ NSCLC in China (N=173) and globally (N=189), respectively. The primary endpoint of both studies is confirmed objective response rate as assessed by an independent review committee. TRUST-IV (NCT07154706) is a phase 3 placebo-controlled study evaluating IBTROZI for the adjuvant treatment of adults with resected early-stage ROS1+ NSCLC, planning to enroll approximately 180 patients in the U.S., Canada, Europe, Japan, and China, with disease-free survival by investigator as the primary endpoint and an estimated primary completion date in 2030. Nuvation Bio is also sponsoring TRUST-III (NCT06564324), a confirmatory randomized phase 3 study evaluating IBTROZI versus crizotinib in 194 patients in China with advanced ROS1+ NSCLC who have not previously received ROS1 TKIs.
Regulatory History and Global Reach
The FDA granted full approval to IBTROZI in June 2025 for the treatment of locally advanced or metastatic ROS1 (搜索)+ NSCLC across lines of therapy, following Priority Review and Breakthrough Therapy designations for both TKI-naive and TKI-pretreated disease. The FDA accepted the current sNDA in May 2026. Outside the United States, IBTROZI is approved for patients with advanced ROS1+ NSCLC in Japan, where it is marketed by Nippon Kayaku (搜索), and in China, where it is marketed by Innovent Biologics (搜索) under the brand name DOVBLERON. Nuvation Bio and its partner Eisai announced in March 2026 that the Marketing Authorisation Application (MAA) for taletrectinib was validated by the European Medicines Agency (搜索) (EMA) for full approval consideration under a standard review timeline, and in June 2026 that the MAA was validated by the Medicines and Healthcare products Regulatory Agency (搜索) (MHRA) in the United Kingdom.
Safety Profile
IBTROZI is described as an oral, potent, CNS-active, selective, next-generation ROS1 (搜索) inhibitor. In the updated safety information, the most frequently reported adverse reactions (≥20%) were diarrhea (64%), nausea (47%), vomiting (43%), dizziness (22%), rash (22%), constipation (21%), and fatigue (20%). The most frequently reported grade 3/4 laboratory abnormalities (≥5%) were increased ALT (13%), increased AST (10%), decreased neutrophils (5%), and increased creatine phosphokinase (5%).
The label carries warnings and precautions for hepatotoxicity, including drug-induced liver injury and fatal adverse reactions: 88% of patients experienced increased AST, including 10% grade 3/4, and 85% experienced increased ALT, including 13% grade 3/4, with fatal liver events in 0.6% of patients. Median time to first onset of AST or ALT elevation was 15 days (range, 3 days to 20.8 months). Interstitial lung disease (ILD)/pneumonitis occurred in 2.3% of patients, including 1.1% grade 3/4, with one fatal ILD case at the 400 mg daily dose and a median time to first onset of 3.8 months (range, 12 days to 11.8 months). QTc interval prolongation is also flagged: among patients with at least one post-baseline ECG, a QTcF increase of more than 60 msec from baseline and QTcF greater than 500 msec occurred in 13% and 2.6% of patients, respectively, and 3.4% experienced grade ≥3 events. Hyperuricemia was reported in 14% of patients, myalgia in 10%, and skeletal fractures in 3.4%, including 1.4% grade 3. The label advises administering IBTROZI on an empty stomach and avoiding concomitant use with strong and moderate CYP3A inhibitors, CYP3A inducers, drugs with a known potential to prolong the QTc interval, and proton pump inhibitors or H2 receptor antagonists.
Disease Burden in ROS1+ NSCLC
More than one million people globally are diagnosed with NSCLC each year, the most common form of lung cancer, and approximately 2% of patients with NSCLC have ROS1 (搜索)+ disease. About 35% of patients newly diagnosed with metastatic ROS1+ NSCLC have tumors that have spread to the brain, and the brain is the most common site of disease progression, with about 50% of previously treated patients developing central nervous system metastases.
Nuvation Bio, founded in 2018, describes its pipeline as including taletrectinib, the brain-penetrant IDH1 (搜索) inhibitor safusidenib, and an innovative drug-drug conjugate (DDC) program.