Taletrectinib

Brand Names: Ibtrozi

Drug Class: General Prescription

Overview

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•C 6 H 10 O 4 and the molecular weight is 551.61 g/mol. The chemical name is 3-{4-[(2 R )-2-aminopropoxy]phenyl}- N -[(1 R )-1-(3-fluorophenyl)ethyl]imidazo [1,2 b ]pyridazin-6-amine monoadipate.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Taletrectinib is an inhibitor of tyrosine kinase ROS1, including ROS1 resistance mutations. Taletrectinib also showed inhibitory effects on tropomyosin receptor kinases (TRKs) TRKA, TRKB, and TRKC. Fusion proteins that include ROS1 domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Taletrectinib inhibited growth of cancer cells expressing ROS1 fusion genes and mutations. In mice subcutaneously implanted with tumors harboring ROS1 fusions, including the G2032R mutation, administration of taletrectinib resulted in tumor growth inhibition. Taletrectinib had anticancer activity in an intracranial NSCLC xenograft model harboring a ROS1 fusion. 12.

Indications

  • 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 )

Common Doses

  • 600 mg
  • 400 mg
  • 200 mg

Dosage

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 )] .

Contraindications

  • 4 CONTRAINDICATIONS None. None ( 4 )

Side Effects

  • 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.

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.