Taletrectinib
FDA Drug Information • Also known as: Ibtrozi
- Brand Names
- Ibtrozi
- Dosage Form
- CAPSULE
- Product Type
- DRUG FOR FURTHER PROCESSING
Description
11 DESCRIPTION IBTROZI (taletrectinib) capsules contain taletrectinib adipate, a kinase inhibitor for oral use. The molecular formula for taletrectinib adipate is C 23 H 24 FN 5 O
What Is Taletrectinib Used For?
1 INDICATIONS AND USAGE IBTROZI ™ (taletrectinib) is indicated for the treatment of adult patients with locally advanced or metastatic ROS1 -positive non-small cell lung cancer (NSCLC) [see Dosage and Administration ( 2.1 )] . IBTROZI is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic ROS1 -positive non-small cell lung cancer (NSCLC). ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Select patients for the treatment of locally advanced or metastatic NSCLC based on the presence of ROS1 rearrangement(s). ( 2.1 ) Recommended Dosage: 600 mg orally once daily on an empty stomach (no food intake at least 2 hours before and 2 hours after taking IBTROZI). ( 2.3 ) Continue treatment until disease progression or unacceptable toxicity. ( 2.3 ) 2.1 Patient Selection Select patients for the treatment of locally advanced or metastatic NSCLC with IBTROZI based on the presence of ROS1 rearrangement(s) in tumor specimens [see Clinical Studies ( 14.1 )] . An FDA-approved test to detect ROS1 rearrangement(s) for selecting patients for treatment with IBTROZI is not currently available. 2.2 Recommended Testing and Evaluation Before Initiating IBTROZI Before initiating IBTROZI, evaluate liver function tests (including ALT, AST, and bilirubin), electrolytes, ECG, and uric acid [see Warnings and Precautions ( 5.1 , 5.3 , 5.4 )]. 2.3 Recommended Dosage and Administration The recommended dosage of IBTROZI is 600 mg orally once daily on an empty stomach (no food intake at least 2 hours before and 2 hours after taking IBTROZI) [see Clinical Pharmacology ( 12.2 , 12.3 )] until disease progression or unacceptable toxicity. Take IBTROZI at approximately the same time each day. Swallow IBTROZI capsules whole. Do not open, chew, crush, or dissolve the capsule prior to swallowing. Avoid food or drink containing grapefruit during treatment with IBTROZI. Minimize sun exposure and use sun protection, including broad-spectrum sunscreen, during treatment with IBTROZI and for at least 5 days after discontinuation [see Adverse Reactions ( 6.1 )]. Missed Dose If a dose is missed, take the next dose at its scheduled time on the following day. Vomiting If vomiting occurs at any time after taking a dose, take the next dose at its scheduled time on the following day. 2.4 Dosage Modifications for Adverse Reactions The recommended dosage reductions for the management of adverse reactions are provided in Table 1 . Table 1: Recommended Dose Reductions for IBTROZI Adverse Reactions Dosage Reduction Recommended Dosage First Dose Reduction 400 mg once daily Second Dose Reduction 200 mg once daily Permanently discontinue IBTROZI capsules in patients unable to tolerate 200 mg once daily. The recommended dosage modifications of IBTROZI for the management of adverse reactions are provided in Table 2 . Table 2: Recommended Dosage Modifications for IBTROZI Adverse Reactions Adverse Reaction Severity* Dosage Modification Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = Upper limit of normal *Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Hepatotoxicity (Elevation of ALT or AST) [see Warnings and Precautions ( 5.1 )] Grade 3 (>5 - 20 × ULN) Withhold IBTROZI until recovery to Grade ≤1 or baseline. If resolved within 6 weeks, resume IBTROZI at a reduced dose...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in the WARNINGS AND PRECAUTIONS section: Hepatotoxicity [see Warnings and Precautions ( 5.1 )] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions ( 5.2 )] QTc Interval Prolongation [see Warnings and Precautions ( 5.3 )] Hyperuricemia [see Warnings and Precautions ( 5.4 )] Myalgia with Creatine Phosphokinase Elevation [see Warnings and Precautions ( 5.5 )] Skeletal fractures [see Warnings and Precautions ( 5.6 )] The most frequently reported adverse reactions (≥20%) were: diarrhea, nausea, vomiting, dizziness, rash, constipation, and fatigue. ( 6.1 ) The most frequently reported Grade 3 or 4 laboratory abnormalities (≥5%) were: increased ALT, increased AST, decreased neutrophils, and increased creatine phosphokinase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Nuvation Bio Inc. at 1-844-688-4550 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS section and below reflects exposure to IBTROZI as a single agent at 600 mg orally once daily until disease progression or unacceptable toxicity in 352 patients with ROS1 -positive NSCLC (N=337) and other solid tumors (N=15). Among the 352 patients who received IBTROZI, 68% were exposed for at least 6 months, and 47% were exposed for greater than 1 year. In this pooled safety population, the most common (≥20%) adverse reactions were diarrhea, nausea, vomiting, dizziness, rash, constipation, and fatigue. The most common (≥2%) Grade 3 or 4 laboratory abnormalities were increased ALT, increased AST, decreased neutrophils, increased creatine phosphokinase, decreased lymphocytes, increased magnesium, decreased hemoglobin, and increased triglycerides. Locally Advanced or Metastatic ROS1-Positive NSCLC The safety of IBTROZI was evaluated in the TRUST-I and TRUST-II studies [see Clinical Studies ( 14.1 )]. Key eligibility criteria were histologically confirmed, locally advanced or metastatic, ROS1 -positive NSCLC, ECOG performance status ≤1, and measurable disease per RECIST v1.1. Patients received IBTROZI as a single agent at 600 mg orally once daily until disease progression or unacceptable toxicity. Among patients who received IBTROZI, 68% were exposed for 6 months or longer and 47% were exposed for greater than one year. The median age of patients who received IBTROZI was 56 years (range: 26 to 83); 56% female; 76% Asian, 15% White, 0.6% Black or African American, 8% unknown or other races; and 1.8% were of Hispanic or Latino ethnicity. Serious adverse reactions occurred in 31% of patients who received IBTROZI. Serious adverse reactions in ≥2% of patients included pneumonia (7%), pleural effusion (4.7%), and hepatotoxicity (2.4%). Fatal adverse reactions occurred in 18 (5%) patients who received IBTROZI, including pneumonia (2.4%), multiple organ dysfunction syndrome (0.6%), hepatotoxicity (0.6%), cardiac arrest (0.6%), cardiac failure (0.3%), cardiopulmonary failure (0.3%), respiratory failure (0.3%), and death not otherwise specified (0.3%). Permanent discontinuation of IBTROZI was required in 7% of patients due to adverse reactions. Adverse reactions resulting in permanent discontinuation of IBTROZI in ≥2 patients were pneumonia, ILD, and hepatotoxicity. Dosage interruptions of IBTROZI due to an adverse reaction occurred in 41% of patients. Adverse reactions which required dosage interruption in ≥5% of patients included increased AST and increased ALT. Dose reductions of IBTROZI due to an adverse reaction occurred in 29% of patients. Adverse reactions that required dosage reductions in ≥5% of patients included...
Drug Interactions
7 DRUG INTERACTIONS Strong and Moderate CYP3A inhibitors : Avoid concomitant use. ( 7.1 ) Strong and Moderate CYP3A inducers: Avoid concomitant use. ( 7.1 ) Gastric Acid Reducing Agents: Avoid concomitant use with proton pump inhibitors (PPIs) and H2 receptor antagonists. If an acid-reducing agent cannot be avoided, administer IBTROZI 2 hours before or 2 hours after taking a locally acting antacid. ( 7.1 ) Drugs That Prolong the QTc Interval: Avoid concomitant use. ( 7.2 ) 7.1 Effects of Other Drugs on IBTROZI Strong and Moderate CYP3A Inhibitors Avoid concomitant use with strong or moderate CYP3A inhibitors. Taletrectinib is a CYP3A substrate. Concomitant use of IBTROZI with a strong or moderate CYP3A inhibitor increases taletrectinib exposure [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of IBTROZI adverse reactions. Strong and Moderate CYP3A Inducers Avoid concomitant use with strong or moderate CYP3A inducers. Concomitant use of IBTROZI with a strong or moderate CYP3A inducer decreases taletrectinib exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce the effectiveness of IBTROZI. Gastric Acid Reducing Agents Avoid concomitant use with proton pump inhibitors (PPI) and H2 receptor antagonists. Administer locally acting antacids at least 2 hours before or 2 hours after taking IBTROZI [see Clinical Pharmacology ( 12.3 )]. Concomitant use of a proton pump inhibitor decreases taletrectinib exposure [see Clinical Pharmacology ( 12.3 )], which may reduce the effectiveness of IBTROZI. 7.2. Drugs That Prolong the QTc Interval Avoid concomitant use of IBTROZI with other drug(s) with a known potential to prolong the QTc interval, such as antiarrhythmic drugs. If concomitant use cannot be avoided, adjust the frequency of monitoring as recommended [see Warnings and Precautions ( 5.3 ), Clinical Pharmacology ( 12.2 )]. Withhold IBTROZI if the QTc interval is >500 msec or the change from baseline is >60 msec [see Dosage and Administration ( 2.4 )]. IBTROZI causes QTc interval prolongation [see Warnings and Precautions ( 5.3 ), Clinical Pharmacology ( 12.2 )] . Concomitant use of IBTROZI with other drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.
Contraindications
4 CONTRAINDICATIONS None. None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , IBTROZI can cause fetal harm when administered to a pregnant woman. Limited data from case reports with IBTROZI used in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, oral administration of taletrectinib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal mortalities and structural abnormalities at exposures that were below or equal to the human exposure based on AUC at the recommended dose ( see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis. Animal Data In an embryo-fetal development study, taletrectinib was administered orally to pregnant rats during the period of organogenesis from gestation day 6 to 17 at doses of 10, 30, and 100 mg/kg/day. Taletrectinib caused fetal abnormalities including abnormal ossification of the pelvis at 100 mg/kg/day (1.3 times the human exposure based on AUC at the recommended dose). In an embryo-fetal development study, taletrectinib was administered orally to pregnant rabbits during the period of organogenesis from gestation day 6 to 19 at doses of 15, 30, and 90 mg/kg/day. Maternal lethality and increased total pregnancy loss were observed at doses ≥15 mg/kg/day (≥0.04 times the human exposure based on AUC at the recommended dose). Fetal...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING IBTROZI is supplied as 200 mg, Size 0 white opaque hard capsules imprinted with “TAL” and “200” in blue ink in bottles of 30 capsules (NDC 84651-200-30) in a carton containing three bottles of 30 count for a total of 90 capsules per carton (NDC 84651-200-93). Store IBTROZI at 20°C to 25°C (68°F to 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F) [ see USP Controlled Room Temperature ].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.