U.S. Food and Drug Administration Approves Nuvation Bio’s IBTROZI™ (taletrectinib), a Next-Generation Oral Treatment for Advanced ROS1-Positive Non-Small Cell Lung Cancer
Approval follows Priority Review and is supported by the robust TRUST clinical program, in which IBTROZI treatment demonstrated high, durable response rates and brain-penetrant efficacy across different lines of therapy
The safety and tolerability of IBTROZI have been well established in the pivotal program, with one of the largest safety datasets in ROS1+ NSCLC showing a favorable and consistent profile
Company to host conference call tomorrow,
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“The FDA approval of IBTROZI marks a major milestone in the evolution of targeted therapy for advanced ROS1-positive NSCLC,” said
ROS1+ NSCLC is a rare and aggressive form of lung cancer, accounting for approximately 2% of new NSCLC cases, or about 3,000 new diagnoses of advanced disease annually in the
“For people living with advanced ROS1-positive lung cancer, who tend to be diagnosed at a younger age, having another treatment option can make a real difference for them and their loved ones,” said
The FDA approval of IBTROZI is supported by one of the largest global clinical trial programs in ROS1+ NSCLC to date, with over 300 patients enrolled in the pivotal TRUST-I and TRUST-II studies.
In TRUST-I, IBTROZI achieved a confirmed overall response rate (cORR) of 90% in TKI-naïve patients. These findings were reinforced by the TRUST-II results, with a cORR of 85% in TKI-naïve patients. The median duration of response (DOR) was not yet reached for either trial, based on a cutoff date that is nearly five months later than that of the pooled TRUST-I and TRUST-II analysis published in April in the
Across the pivotal studies, consistent results were also observed among patients who were previously treated with a ROS1 TKI (TKI-pretreated). In TRUST-I, treatment with IBTROZI achieved a cORR of 52% and median DOR of 13.2 months for TKI-pretreated patients, with median follow-up for responses of 33 months. In TRUST-II, treatment with IBTROZI achieved a cORR of 62%, and as of
Brain metastases are among the most common and devastating complications in advanced ROS1+ NSCLC. IBTROZI was designed to penetrate the central nervous system (CNS) and has demonstrated consistent intracranial responses in patients with measurable brain metastases at baseline. An intracranial response was achieved in 73% of TKI-naive patients (11/15) and 63% of TKI-pretreated patients (15/24).
“Patients living with advanced ROS1+ non-small cell lung cancer and their healthcare providers are in need of new treatment options,” added
IBTROZI was generally well-tolerated, with most adverse events being low grade, transient and manageable. Patients infrequently (7%) discontinued treatment due to treatment-emergent adverse events (TEAEs). The most common adverse reactions (≥20%) included diarrhea (64%), nausea (47%), vomiting (43%), dizziness (22%), rash (22%), constipation (21%), and fatigue (20%). Overall, the majority of CNS events were mild to moderate (~90%) and resolved within days, and dose modifications due to these events were low (~5%). Approximately 90% of reported cases of dizziness were Grade 1 (mild) and transient. Liver enzyme elevations (AST 87%/ALT 85%) and QT prolongation (19%) were manageable with standard monitoring and dose modifications. IBTROZI is approved as a 600 mg once-daily oral dose, supported by a half-life of approximately 66 hours and broad tissue distribution, including the brain, enabling sustained systemic and CNS exposure.
Conference Call & Business Update
As a reminder to investors, the approval, together with the first commercial sale, makes the funding secured from
Investors and the general public are invited to register and listen to a live webcast of the event through the company website at https://investors.nuvationbio.com. Those unable to register can access the live conference call by dialing +1 833-470-1428 (
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 35% of patients newly diagnosed with metastatic ROS1+ NSCLC have tumors that have spread to their brain. The brain is also the most common site of disease progression, with about 50% of previously treated patients developing CNS metastases. Despite recent progress for patients with ROS1+ NSCLC, there remains a need for more effective and tolerable treatment options.
About IBTROZI
IBTROZI is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor therapy approved for the treatment of adult patients with advanced ROS1-positive non-small cell lung cancer. Learn more at IBTROZI.com.
About the TRUST Clinical Program
The TRUST clinical program evaluating IBTROZI for the treatment of adult patients with advanced ROS1+ NSCLC included two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in
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.
Please see accompanying full Prescribing Information .
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Forward-Looking Statements
Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements are sometimes accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, our expectations regarding IBTROZI’s therapeutic potential in advanced ROS1+ NSCLC and its potential to become a new standard of care. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the management team of
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