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IBTROZI™ (taletrectinib) logo
IBTROZI™ (taletrectinib) logo

What is ROS1+ NSCLC?

Efficacy

TKI-naïveTKI-pretreatedStudy design

Safety

Safety overviewLaboratory abnormalitiesDose modification ratesOnset and resolution

Dosing

Recommended dosingDose reductionsDrug interactionsDose modificationsMonitoring

Support and access

Patient support programDistribution information

Resources

HCP resourcesPatient and caregiver resources

IBTROZI delivered a strong and sustained response in TKI-naïve patients1,2

TRUST-I (n=103)1,2

90% ORR

(95% CI: 83–95) 85% PR, 5% CR

Median follow-up time for response: 40 months (range: 19.9 to 48.7)

TRUST-I trial Kaplan Meier curve. Median Duration of Response not reached

*“+” indicates an ongoing response.

TRUST-I and TRUST-II are ongoing and DOR results are subject to change as the data mature.

  • 72% of responders had an observed DOR of ≥12 months
  • In responding patients, the longest DOR observed was 46.9 months, with response ongoing (range: 1.1 to 46.9+)

TRUST-II (n=54)1,2

85% ORR

(95% CI: 73–93) 78% PR, 7% CR

Median follow-up time for response: 19 months (range: 10.6 to 33.1)

TRUST-II trial Kaplan Meier curve. Median Duration of Response not reached

†“+” indicates an ongoing response.

TRUST-I and TRUST-II are ongoing and DOR results are subject to change as the data mature. mDOR for TRUST-II is not reported in the PI due to shorter duration of follow-up.

  • 63% of responders had an observed DOR of ≥12 months
  • In responding patients, the longest DOR observed was 30.4 months, with response ongoing (range: 1.4+ to 30.4+)

TRUST-I and TRUST-II1

Clinically meaningful CNS response in TKI-naïve patients

73% (n=11/15)

of patients with CNS metastases saw an intracranial response

TRUST-I and TRUST-II study information

The efficacy of IBTROZI was evaluated in 270 TKI-naïve or TKI-pretreated patients with ROS1+ NSCLC who received IBTROZI 600 mg once daily, enrolled in 2 multicenter, single-arm, open-label clinical trials. Patients were required to have histologically confirmed, locally advanced or metastatic, ROS1+ NSCLC with an ECOG PS ≤1, and measurable disease per RECIST v1.1. The primary and key secondary endpoints were confirmed ORR and DOR according to RECIST v1.1, as assessed by BICR. All patients were either chemotherapy naïve or had received prior chemotherapy for locally advanced disease.1

SELECT SAFETY INFORMATION

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.

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.

Monitor liver function tests prior to treatment, every 2 weeks during the first 2 months, then monthly thereafter as clinically indicated. Test more frequently if transaminase elevations occur. Based on severity and resolution, withhold, then resume at a reduced dose or permanently discontinue.

IBTROZI delivered notable response in patients who received prior TKI treatment1,2

TRUST-I and TRUST-II1,2

TRUST-I (n=66)

Median follow-up time for response: 33 months
(range: 20.2 to 46.0)

52% ORR

(95% CI: 39–64)
52% PR, 0% CR

  • 74% of responders had an observed DOR of ≥6 months
  • 44% of responders had an observed DOR of ≥12 months

TRUST-II (n=47)

Median follow-up time for response: 19 months
(range: 8.0 to 32.2)

62% ORR

(95% CI: 46–75)
51% PR, 11% CR

  • 83% of responders had an observed DOR of ≥6 months
  • 45% of responders had an observed DOR of ≥12 months

TRUST-I and TRUST-II are ongoing and DOR results are subject to change as the data mature. mDOR for TRUST-II is not reported in the PI due to shorter duration of follow-up.

Tumor responses were observed in patients with CNS metastases and resistance mutations who received prior TKI treatment1

TRUST-I and TRUST-II1-3

63% (n=15/24)

of patients with CNS metastases saw an intracranial response

53% (n=8/15)

of patients with acquired resistance mutations saw a response

  • Responses observed in 62% (8/13) patients with G2032R resistance mutations2
  • Solvent front mutation G2032R is the most common on-target resistance mutation in crizotinib-treated patients1,3

SELECT SAFETY INFORMATION

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.

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.

Monitor patients for new or worsening pulmonary symptoms. If ILD/pneumonitis is suspected, immediately withhold; based on severity and resolution, resume at same or reduced dose, or permanently discontinue.

IBTROZI: evaluated in a large population across 2 pivotal trials1,3

More than 300 patients were enrolled in 2 multicenter, single-arm, open-label phase 2 pivotal studies (TRUST-I and TRUST-II) to evaluate the safety and efficacy of IBTROZI, a selective, brain-penetrant TKI. The results were generated in TKI-naïve and TKI-pretreated patients with ROS1+ NSCLC.1,3

PIVOTAL PHASE 2 TRUST TRIALS1,3-5

Key eligibility criteria in TRUST-I and TRUST-II

Inclusion

  • Locally advanced or metastatic NSCLC with confirmed ROS1 fusion
  • ≥1 measurable lesion per RECIST v1.1
  • ECOG PS 0-1
  • Stable CNS involvement was allowed
  • ROS1 TKI treatment naïve or received 1 prior ROS1 TKI

Exclusion

  • Active infection (including active hepatitis B or C)
  • Antitumor drugs ≤14 days
  • Radiotherapy ≤14 days
  • Major surgery ≤4 weeks
  • History of ILD or drug-induced pneumonitis

TRUST-I (N=169)

(taletrectinib 600 mg once daily)

TRUST-II (N=101)

(taletrectinib 600 mg once daily)

TKI-naïve cohort (n=103)TKI-pretreated cohort (n=66)
TKI-naïve cohort (n=54)TKI-pretreated cohort (n=47)

Endpoints in TRUST-I and TRUST-II

Primary endpoint

  • BICR-assessed confirmed ORR per RECIST v1.1

Secondary endpoints

  • DOR, IC-ORR per modified RECIST v1.1, PFS, safety
  • The efficacy-evaluable population (N=270) included patients with ROS1+ NSCLC with ≥1 measurable lesion at baseline per RECIST v1.1 by BICR and who received ≥1 dose of taletrectinib
  • The TRUST-I/TRUST-II safety population (N=337) included patients who were exposed to IBTROZI as a single agent dosed at 600 mg orally once daily until disease progression or unacceptable toxicity
  • A pooled safety population (N=352), described in the Warnings and Precautions section of the Prescribing Information, included 337 patients with ROS1+ NSCLC and 15 patients with solid tumors who received IBTROZI 600 mg once daily

PATIENT CHARACTERISTICS FOR TRUST-I AND TRUST-II1

TRUST-ITRUST-II
PATIENT
POPULATION		TKI-NAÏVE (n=103)TKI-PRETREATED (n=66)TKI-NAÏVE (n=54)TKI-PRETREATED (n=47)
Median age,
years (range)		56 (26-78)51 (31-77)57 (27-82)55 (27-79)
Male/female45%/55%39%/61%44%/56%43%/57%
ECOG PS 181%71%61%55%
Asian100%100%65%47%
White0%0%22%34%
Black or African American0%0%1.9%2.1%
Unknown or other races0%0%11%17%
Hispanic or LatinoNANA1.9%2.1%
Never smoked73%74%50%62%
Adenocarcinoma histology96%92%98%98%
Prior platinum-based chemotherapy19%35%19%40%
Prior crizotinibNA100%NA79%
Prior entrectinibNA0%NA21%
Metastatic disease at baseline91%97%91%98%
CNS metastastes at baseline17%42%35%57%
< What is ROS1+ NSCLC?Safety >

INDICATION

IBTROZI™ (taletrectinib) is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

IMPORTANT SAFETY INFORMATION

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.

Monitor liver function tests (AST, ALT, and bilirubin) prior to treatment, every 2 weeks during the first 2 months, and then monthly thereafter as clinically indicated. Test more frequently if transaminase elevations occur. Advise patients to immediately report symptoms of hepatotoxicity. Based on severity and resolution, withhold, then resume at a reduced dose or permanently discontinue.

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.

Monitor patients for new or worsening pulmonary symptoms. Advise patients to report symptoms. If ILD/pneumonitis is suspected, immediately withhold; based on severity and resolution, resume at same or reduced dose, or permanently discontinue.

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.

Monitor ECGs and electrolytes prior to start of therapy, and then periodically thereafter as clinically indicated. Adjust frequency based on risk factors such as known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, and concomitant medications.

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.

Advise patients to immediately report any symptoms of QT interval prolongation. Based on severity and resolution, withhold, then resume at same or reduced dose, or permanently discontinue.

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.

Monitor serum uric acid levels prior to initiating and periodically during treatment. Initiate urate-lowering medications as clinically indicated. Advise patients to report symptoms. Based upon severity and resolution, withhold, then resume at same or reduced dose, or permanently discontinue.

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.

Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor serum CPK levels during treatment every 2 weeks during the first month, and then as clinically indicated. Based on severity, withhold, then resume at same or reduced dose upon improvement.

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 such as osteoporosis, bone metastasis, and age-related degenerative conditions. 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.

Advise patients to immediately report symptoms. Promptly evaluate patients with signs or symptoms (e.g., pain, changes in mobility, deformity) of fractures.

There are no data on the effects of IBTROZI on healing of known fractures and risk of future fractures.

Embryo-Fetal Toxicity: Based on literature, animal studies, and its mechanism of action, IBTROZI can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating IBTROZI. Advise females to inform their healthcare provider of a known or suspected pregnancy.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks following the last dose.

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: Avoid concomitant use.
  • Strong and Moderate CYP3A Inducers: 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.
  • Drugs that Prolong the QTc Interval: Avoid concomitant use. If concomitant use cannot be avoided, adjust the frequency of monitoring as recommended. Withhold IBTROZI if the QTc interval is >500 msec or the change from baseline is >60 msec.

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.

BICR=blinded independent central review; CI=confidence interval; CNS=central nervous system; CR=complete response; DOR=duration of response; ECOG=Eastern Cooperative Oncology Group; IC-mDOR=intracranial median duration of response; IC-ORR=intracranial overall response rate; ILD=interstitial lung disease; mDOR=median duration of response; mPFS=median progression-free survival; NA=not applicable; NR=not reached; NSCLC=non-small cell lung cancer; ORR=overall response rate; PFS=progression-free survival; PI=prescribing information; PR=partial response; PS=performance status; RECIST=Response Evaluation Criteria in Solid Tumors; ROS1=ROS proto-oncogene 1; TKI=tyrosine kinase inhibitor.

References: 1. IBTROZI™ (taletrectinib). Prescribing Information. Nuvation Bio Inc.; 2025. 2. Data on file. Nuvation Bio Inc. 3. Pérol M, Li W, Pennell NA, et al. J Clin Oncol. 2025;JCO2500275:1-10. 4. A study of AB-106 in subjects with advanced NSCLC harboring ROS1 fusion gene. ClinicalTrials.gov identifier: NCT04395677. Updated October 30, 2023. Accessed April 22, 2025. https://clinicaltrials.gov/study/NCT04395677 5. Taletrectinib phase 2 global study in ROS1 positive NSCLC (TRUST-II). ClinicalTrials.gov identifier: NCT04919811. Updated November 21, 2024. Accessed April 22, 2025. https://clinicaltrials.gov/study/NCT04919811