AUGTYRO

The geometric mean (CV%) of repotrectinib steady state peak concentration (C max,ss ) is 713 (32.5%) ng/mL and the area under the time concentration curve (AUC 0-24h,ss ) is 7210 (40.1%) ng

• h/mL following the approved recommended twice daily dosage in patients with cancer. Repotrectinib C max and AUC 0-inf increases approximately dose proportional (but less than linear with estimated slopes of 0.78 and 0.70, respectively) over the single dose range of 40 mg to 240 mg (0.25 to 1.5 times the appro...

14.1 Locally Advanced or Metastatic ROS1 -Positive NSCLC The efficacy of AUGTYRO was evaluated in TRIDENT-1, a multicenter, single-arm, open-label, multi-cohort clinical trial (NCT03093116). Patients were required to have ROS1- positive locally advanced or metastatic NSCLC, ECOG performance status ≤1, measurable disease per RECIST v 1.1, and ≥8 months from first dose. All patients were assessed for CNS lesions at baseline, and patients with symptomatic brain metastases were excluded from the trial. Patients received AUGTYRO 160 mg orally once daily for 14 days, then increased to 160 mg twice d...

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Central Nervous System Adverse Reactions [see Warnings and Precautions (5.1) ]
• Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2) ]
• Hepatotoxicity [see Warnings and Precautions (5.3) ]
• Myalgia with Creatine Phosphokinase Elevation [see Warnings and Precautions (5.4) ]
• Hyperuricemia [see Warnings and Precautions (5.5) ]
• Skeletal Fractures [see Warnings and Preca...

None. None.

• Central Nervous System (CNS) Effects: Can cause CNS adverse reactions including dizziness, ataxia, and cognitive impairment. Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue AUGTYRO based on severity. ( 5.1 )
• Interstitial Lung Disease (ILD)/Pneumonitis: Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumoniti...

7 DRUG INTERACTIONS

• Strong and Moderate CYP3A Inhibitors : Avoid concomitant use. ( 7.1 )
• P-gp inhibitors : Avoid concomitant use. ( 7.1 )
• Strong and Moderate CYP3A Inducers : Avoid concomitant use. ( 7.1 )
• Certain CYP3A Substrates : Avoid concomitant use with CYP3A substrates, where minimal concentration changes can cause reduced efficacy. ( 7.2 )
• Hormonal contraceptives : Avoid concomi...