FDA Approves Hernexeos for HER2-Mutant Non-Small Cell Lung CancerFDA approves new pill Hernexeos for certain lung cancer patients

Not reported in label.

Hernexeos is indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The recommended dosage of Hernexeos is based on body weight: patients weighing less than 90 kg: 120 mg; patients weighing 90 kg or greater: 180 mg. Take orally once daily with or without food until disease progression or unacceptable toxicity. Swallow tablets whole with water; do not split, crush, or chew. If a dose is missed within 12 hours, take the dose; if missed by more than 12 hours, skip the missed dose and take the next scheduled dose. If a dose is vomited, do not take an additional dose; take the next dose at the regularly scheduled time. Dose reductions for adverse reactions are specified in Table 1 of the label. Dosage modifications for adverse reactions include: for Grade 3 or 4 ALT/AST without increased total bilirubin, interrupt until recovery then resume at reduced dose; for Grade 3 total bilirubin, interrupt until recovery then resume at reduced dose; for Grade 4 total bilirubin, permanently discontinue; for ALT or AST ≥3× ULN with total bilirubin ≥2× ULN, permanently discontinue. For left ventricular dysfunction, specific criteria are provided for interruption and resumption or permanent discontinuation. For interstitial lung disease/pneumonitis, Grade 2: withhold until resolution, resume at reduced dose, permanently discontinue for recurrent ILD/pneumonitis; Grade 3 or 4: permanently discontinue. For diarrhea, Grade 2: maintain dose and initiate anti-diarrheal treatment; Grade 2 lasting ≥2 days despite treatment: interrupt until recovery, resume at reduced dose; Grade 3 or 4: interrupt until recovery, resume at reduced dose, permanently discontinue if not resolved within 14 days. For other adverse reactions, Grade 3: interrupt until recovery, resume at reduced dose; Grade 4: permanently discontinue. For strong CYP3A inducers, avoid concomitant use; if unavoidable, increase the dose based on body weight (specific instructions in label).

Trial data not available in label.

Warnings and precautions include hepatotoxicity, left ventricular dysfunction, and interstitial lung disease/pneumonitis. Specific monitoring and management instructions are provided in the label. No contraindications are listed in the label.

Hernexeos provides a targeted treatment option for patients with HER2-mutant non-squamous NSCLC, a population with limited targeted therapies. As an accelerated approval, its clinical benefit is still being verified in confirmatory trials. It should be used in patients whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations as detected by an FDA-authorized test.