On September 30, 2025 Nuvation Bio Inc. (NYSE: NUVB), a global oncology company focused on tackling some of the toughest challenges in cancer treatment, reported it has enrolled the first patient in TRUST-IV (NCT07154706), a Phase 3 study evaluating the efficacy and safety of IBTROZI (taletrectinib), a next-generation ROS1 inhibitor, versus placebo for the adjuvant treatment of patients with resected ROS1-positive (ROS1+) early-stage non-small cell lung cancer (NSCLC) (Press release, Nuvation Bio, SEP 30, 2025, View Source [SID1234656362]).
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"While surgical resection is a standard treatment for early-stage non-small cell lung cancer, many patients will unfortunately have a recurrence of their cancer after surgery. Patients with ROS1 fusion-positive cancers need new options in the adjuvant setting beyond chemotherapy, especially as we have seen improved outcomes with targeted therapies in other driver-positive cancers," said Alexander Drilon, M.D., Chief, Early Drug Development, Memorial Sloan Kettering Cancer Center and trial investigator. "With its well-characterized, manageable safety profile and demonstrated efficacy in advanced disease, taletrectinib, I believe, holds promise to help prevent disease recurrence following resection of ROS1 fusion-positive tumors. I look forward to learning more about the potential of taletrectinib in this setting as the trial advances."
Following alignment with the U.S. Food and Drug Administration on study design, TRUST-IV will enroll approximately 180 patients in the U.S., Canada, Europe, Japan and China with ROS1+ stage IB, II or IIIA NSCLC who have received surgery for their disease. Patients must not have received adjuvant anticancer therapy except standard postoperative platinum-based doublet chemotherapy. Patients will be randomized 2:1 to receive either taletrectinib or placebo daily. The primary endpoint is disease-free survival as determined by investigator. Primary completion date is estimated to be in 2033.
"Based on the proven efficacy and safety data supporting IBTROZI’s use and approval in advanced ROS1-positive non-small cell lung cancer, we are excited to explore its potential in earlier-stage disease, where targeted therapies are lacking," said David Hung, M.D., Founder, President and Chief Executive Officer of Nuvation Bio. "The initiation of this trial, with our first patient in the U.S. now enrolled, marks important momentum with our pipeline as we aim to help more patients with lung cancer stay ahead of their disease."
About ROS1+ NSCLC
Each year, more than one million people globally are diagnosed with non-small cell lung cancer (NSCLC), the most common form of lung cancer. It is estimated that approximately 2% of patients with NSCLC have ROS1+ disease. About 20-30% of patients newly diagnosed with ROS1+ NSCLC have early-stage disease amenable to surgical resection.
About IBTROZI
IBTROZI is an oral, potent, CNS-active, selective, next-generation ROS1 inhibitor therapy. On June 11, following Priority Review and Breakthrough Therapy Designations for both first- and second-line treatment, the U.S. Food and Drug Administration (FDA) approved IBTROZI for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC. Learn more at IBTROZI.com.
Indication
IBTROZI is indicated for the treatment of adult patients with locally advanced or metastatic ROS1+ non-small cell lung cancer (NSCLC).
IMPORTANT SAFETY INFORMATION FOR IBTROZITM (taletrectinib)
WARNINGS AND PRECAUTIONS
Hepatotoxicity: Hepatotoxicity, including drug-induced liver injury and fatal adverse reactions, can occur. 88% of patients experienced increased AST, including 10% Grade 3/4. 85% of patients experienced increased ALT, including 13% Grade 3/4. Fatal liver events occurred 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).
Increased AST or ALT each led to dose interruption in 7% of patients and dose reduction in 5% and 9% of patients, respectively. Permanent discontinuation was caused by increased AST, ALT, or bilirubin each in 0.3% and by hepatotoxicity in 0.6% of patients.
Concurrent elevations in AST or ALT ≥3 times the ULN and total bilirubin ≥2 times the ULN, with normal alkaline phosphatase, occurred in 0.6% of patients.
Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, or fatal ILD or pneumonitis can occur. ILD/pneumonitis occurred in 2.3% of patients, including 1.1% Grade 3/4. One fatal ILD case occurred at the 400 mg daily dose. Median time to first onset of ILD/pneumonitis was 3.8 months (range: 12 days to 11.8 months).
ILD/pneumonitis led to dose interruption in 1.1% of patients, dose reduction in 0.6% of patients, and permanent discontinuation in 0.6% of patients.
QTc Interval Prolongation: QTc interval prolongation can occur, which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death. IBTROZI prolongs the QTc interval in a concentration-dependent manner.
In patients who received IBTROZI and underwent at least one post baseline ECG, QTcF increase of >60 msec compared to baseline and QTcF >500 msec occurred in 13% and 2.6% of patients, respectively. 3.4% of patients experienced Grade ≥3. Median time from first dose of IBTROZI to onset of ECG QT prolongation was 22 days (range: 1 day to 38.7 months). Dose interruption and dose reduction each occurred in 2.8% of patients.
Significant QTc interval prolongation may occur when IBTROZI is taken with food, strong and moderate CYP3A inhibitors, and/or drugs with a known potential to prolong QTc. Administer IBTROZI on an empty stomach. Avoid concomitant use with strong and moderate CYP3A inhibitors and/or drugs with a known potential to prolong QTc.
Hyperuricemia: Hyperuricemia can occur and was reported in 14% of patients, with 16% of these requiring urate-lowering medication without pre-existing gout or hyperuricemia. 0.3% of patients experienced Grade ≥3. Median time to first onset was 2.1 months (range: 7 days to 35.8 months). Dose interruption occurred in 0.3% of patients.
Myalgia with Creatine Phosphokinase (CPK) Elevation: Myalgia with or without CPK elevation can occur. Myalgia occurred in 10% of patients. Median time to first onset was 11 days (range: 2 days to 10 months).
Concurrent myalgia with increased CPK within a 7-day time period occurred in 0.9% of patients. Dose interruption occurred in 0.3% of patients with myalgia and concurrent CPK elevation.
Skeletal Fractures: IBTROZI can increase the risk of fractures. ROS1 inhibitors as a class have been associated with skeletal fractures. 3.4% of patients experienced fractures, including 1.4% Grade 3. Some fractures occurred in the setting of a fall or other predisposing factors. Median time to first onset of fracture was 10.7 months (range: 26 days to 29.1 months). Dose interruption occurred in 0.3% of patients.
Embryo-Fetal Toxicity: Based on literature, animal studies, and its mechanism of action, IBTROZI can cause fetal harm when administered to a pregnant woman.
ADVERSE REACTIONS
Among patients who received IBTROZI, 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%).
DRUG INTERACTIONS
Strong and Moderate CYP3A Inhibitors/CYP3A Inducers and Drugs that Prolong the QTc Interval: Avoid concomitant use.
Gastric Acid Reducing Agents: Avoid concomitant use with PPIs and H2 receptor antagonists. If an acid-reducing agent cannot be avoided, administer locally acting antacids at least 2 hours before or 2 hours after taking IBTROZI.
OTHER CONSIDERATIONS
Pregnancy: Please see important information in Warnings and Precautions under Embryo-Fetal Toxicity.
Lactation: Advise women not to breastfeed during treatment and for 3 weeks after the last dose.
Effect on Fertility: Based on findings in animals, IBTROZI may impair fertility in males and females. The effects on animal fertility were reversible.
Pediatric Use: The safety and effectiveness of IBTROZI in pediatric patients has not been established.
Photosensitivity: IBTROZI can cause photosensitivity. Advise patients to minimize sun exposure and to use sun protection, including broad-spectrum sunscreen, during treatment and for at least 5 days after discontinuation.