Nuvation Bio Announces New Data from Pivotal Clinical Studies of IBTROZI™ (taletrectinib) in Advanced ROS1-Positive Non-Small Cell Lung Cancer at 2025 World Conference on Lung Cancer

Sustained durability of responses demonstrated in both TRUST-I and TRUST-II with additional follow-up time

TKI-naïve patients in TRUST-I achieved a median progression-free survival of 44.6 months; more than half of TKI-naïve patients in TRUST-II were still progression-free at data cut-off

The findings showed a favorable safety and tolerability profile for IBTROZI with manageable adverse events

Results are from one of the largest global clinical trial programs in ROS1-positive NSCLC to date, with over 300 patients enrolled in the pivotal TRUST-I and TRUST-II studies

NEW YORK--(BUSINESS WIRE)-- Nuvation Bio Inc. (NYSE: NUVB), a global oncology company focused on tackling some of the toughest challenges in cancer treatment, today announced new and updated results from the pivotal Phase 2 TRUST-I and TRUST-II studies evaluating IBTROZI™ (taletrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC). The new findings are being highlighted in an oral presentation and poster session at the IASLC 2025 World Conference on Lung Cancer (WCLC), taking place September 6 to 9 in Barcelona, Spain.

“With additional follow-up time, these updated findings from the TRUST studies show notable progression-free survival results and demonstrate that responses with IBTROZI remain durable, with a well-characterized, manageable safety profile,” said Geoffrey Liu, M.D., Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto. “The results further support the recent approval of IBTROZI in the U.S., which has added an important new option for a range of patients with this form of lung cancer, regardless of prior exposure to tyrosine kinase inhibitor therapy.”

“Disease progression remains one of the greatest threats to people with advanced ROS1+ non-small cell lung cancer, especially those being treated in the first-line setting,” said David Hung, M.D., Founder, President and Chief Executive Officer of Nuvation Bio. “These long-term data emphasize impressive PFS and durability of response, with a tolerable and manageable safety profile that helps patients stay on therapy so they can continue to benefit. We remain excited about the promise of IBTROZI and look forward to further data generation from continued follow up in the TRUST studies.”

Updated TRUST-II Study Results

Updated efficacy data from the global TRUST-II study as of October 28, 2024, are being presented in a mini oral session on September 7.

For patients in TRUST-II who had not previously been treated with a ROS1 tyrosine kinase inhibitor (TKI-naïve; n=54), confirmed objective response rate (cORR) was 85.2% at a median follow-up of 20.5 months. Median progression-free survival (PFS) was not yet reached, meaning more than half of patients had not progressed, and the longest PFS was observed at 31.6 months and ongoing. Median duration of response (DOR) was also not yet reached; the longest DOR was observed at 30.4 months and ongoing. A DOR of at least 12 months was achieved by 74.0% of patients and of at least 18 months by 68% of patients based on Kaplan-Meier estimates. An intracranial response was achieved by 66.7% (6/9) of patients with brain metastases.

In TKI-pretreated patients (n=47), cORR was 61.7% at a median follow-up of 20.4 months. Median PFS was 11.8 months, and median DOR was 19.4 months. An intracranial response was achieved by 56.3% (9/16) of patients with brain metastases.

Updated TRUST-I Study Results

Updated efficacy data as of October 28, 2024, from the TRUST-I study will be presented in a poster session on September 9.

For TKI-naïve patients in TRUST-I (n=103), cORR was 90.3% at a median follow-up of 40.9 months. Median PFS was 44.6 months. Median DOR was not yet reached; the longest DOR was observed at 46.9 months and ongoing. An intracranial response was achieved by 87.5% (7/8) of patients with brain metastases.

In TKI-pretreated patients (n=66), cORR was 51.5% at a median follow-up of 35.1 months. Median PFS was 7.6 months, and median DOR was 13.2 months. An intracranial response was achieved by 75.0% (12/16) of patients with brain metastases.

Pooled Safety Data from TRUST-I and TRUST-II

Safety characterization in the integrated analysis from across trials (N=337) included in the poster presentation demonstrated a favorable safety and tolerability profile for IBTROZI with manageable adverse events (AEs). AEs of clinical interest (diarrhea, nausea, vomiting and dizziness) were transient and resolved quickly (median resolution range 1-3 days). No treatment discontinuations occurred due to these AEs of clinical interest. AST and ALT elevations occurred in 76% of patients and led to one patient discontinuing treatment.

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 central nervous system (CNS) metastases.

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 or later, 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.

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 China, which enrolled 173 patients, and TRUST-II (NCT04919811), a global study, which enrolled 189 patients. The primary endpoint of these registrational studies is confirmed objective response rate (cORR) as assessed by an independent review committee (IRC). Secondary endpoints include intracranial cORR, duration of response, progression-free survival, and safety.

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 IBTROZI^TM (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.

About Nuvation Bio
Nuvation Bio is a global oncology company focused on tackling some of the toughest challenges in cancer treatment with the goal of developing therapies that create a profound, positive impact on patients’ lives. Our diverse pipeline includes taletrectinib (IBTROZI™), a next-generation ROS1 inhibitor; safusidenib, a brain-penetrant IDH1 inhibitor; NUV-1511, an innovative drug-drug conjugate (DDC) designed for targeted cancer treatment; and NUV-868, a BD2-selective BET inhibitor.

Nuvation Bio was founded in 2018 by biopharma industry veteran David Hung, M.D., who previously founded Medivation, Inc., which brought to patients one of the world’s leading prostate cancer medicines. Nuvation Bio has offices in New York, San Francisco, Boston, and Shanghai. For more information, visit www.nuvationbio.com or follow the company on LinkedIn and X (@nuvationbioinc).

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, statements regarding IBTROZI’s therapeutic potential including with respect to IBTROZI’s mPFS, durability of response, tolerability, safety profile, and the ability for patients to stay on therapy and benefit from IBTROZI. These forward-looking statements are subject to a number of risks and uncertainties that may cause actual results to differ from those anticipated by the forward-looking statements, including but not limited to the challenges associated with conducting drug discovery and commercialization, and initiating or conducting clinical studies due to, among other things, difficulties or delays in the regulatory process, enrolling subjects or manufacturing or acquiring necessary products; the emergence or worsening of adverse events or other undesirable side effects; risks associated with preliminary and interim data, which may not be representative of more mature data; physician and patient behavior; and competitive developments. Risks and uncertainties facing Nuvation Bio are described more fully in its Form 10-Q filed with the SEC on August 7, 2025 under the heading “Risk Factors,” and other documents that Nuvation Bio has filed or will file with the SEC. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Nuvation Bio disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release.

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