TALETRECTINIB CAP,ORAL

Clinical Criteria Summary

Unstable brain metastases
History of prolonged QTc interval (> 450 msec for males or > 470 msec for females)
Prior ROS1, ALK, or NTRK tyrosine kinase inhibitor therapy (except for crizotinib)
Interstitial lung disease, interstitial fibrosis, or lung disease from prior tyrosine kinase inhibitors
Unmanageable drug interactions
Creatinine clearance or eGFR <30 mL/min
Moderate to severe liver dysfunction (Child-Pugh score B/C or NCI Organ Dysfunction Working Group classification unless with Gilbert syndrome)
History of stem cell or organ transplant
Pregnancy
Lactating

Patient with locally advanced or metastatic non-small cell lung cancer whose tumor is ROS1 positive

For females who can become pregnant and males with partners who can become pregnant: Counseling on treatment risks vs benefits and use of effective contraception during and for 3 weeks after last treatment (3 weeks for women, 3 weeks for men)

Locally advanced or metastatic ROS1 fusion positive non-small lung cancer (NSCLC)
Applicable to TKI-naïve and previous crizotinib-pretreated populations

600 mg orally once a day on an empty stomach until disease progression or inacceptable toxicity

Hepatotoxicity: drug-induced liver injury and fatal adverse reactions
Interstitial Lung Disease (ILD)/Pneumonitis: severe, life-threatening, or fatal pulmonary symptoms
QTc Interval Prolongation: increased risk for ventricular tachyarrhythmias or sudden death
Hyperuricemia: increased serum uric acid levels requiring treatment
Myalgia with CPK Elevation: muscle pain with or without enzyme elevation
Skeletal Fractures: increased risk of fractures, including ribs and spine
Embryo-Fetal Toxicity: potential fetal harm

Avoid concomitant use with strong or moderate CYP3A inhibitors and inducers
Avoid concomitant use with proton pump inhibitors (PPIs) and H2 receptor antagonists
Avoid drugs known to prolong the QTc interval
Avoid grapefruit and grapefruit products

Can cause fetal harm when administered to pregnant women
Advise women not to breastfeed during therapy and for 3 weeks after the last dose

NCCN Guidelines list as Preferred 1st line for ROS1 Gene Fusion in NSCLC (alongside crizotinib, entrectinib, repotrectinib)
Recommended as PA-F and replacement of entrectinib with taletrectinib for advanced ROS1 fusion positive NSCLC on the VA Oncology Clinical Pathway for Lung Cancer
Next-generation TKI offering improved progression-free survival, better CNS penetration, and activity against resistance mutations compared to first-generation TKIs
Lower rates of CNS adverse events but higher rates of GI and transaminase elevation compared to other next-generation TKIs