FDA Approves Hyrnuo (zongertinib) for HER2 TKD Mutant Non-Squamous NSCLC After Prior TherapyFDA Approves New Targeted Drug for a Type of Lung Cancer

Hyrnuo is a kinase inhibitor. The specific molecular targets and mechanism are not detailed in the provided label text.

Hyrnuo is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Select patients based on the presence of HER2 (ERBB2) TKD activating mutations in tumor specimens.

The recommended dosage is 20 mg orally twice daily with food, until disease progression or unacceptable toxicity. Swallow tablets whole; do not cut, crush, or chew. If a dose is missed, take it as soon as remembered prior to the next scheduled dose; do not take 2 doses at the same time. If a dose is vomited, do not take an additional dose; resume at the next scheduled time. Dosage reductions for adverse reactions: first reduction to 10 mg twice daily, second to 10 mg once daily; permanently discontinue if unable to tolerate 10 mg once daily. Avoid concomitant use of strong CYP3A inhibitors; if unavoidable, reduce dosage as specified (20 mg twice daily to 10 mg twice daily; 10 mg twice daily to 10 mg once daily; 10 mg once daily: withhold until inhibitor discontinued). After the CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the prior dosage.

The efficacy of Hyrnuo was evaluated in SOHO-01 (NCT05099172), an open-label, single-arm, multicenter, multi-cohort clinical study. Eligible patients (Groups D and E) had previously treated locally advanced or metastatic NSCLC with HER2 (ERBB2) activating mutations and ECOG PS 0 or 1. HER2 activating mutations were determined in tumor tissue or plasma by local laboratories prior to enrollment. Patients with treated, stable, and asymptomatic brain metastases were eligible. The label does not report specific ORR or DOR values; trial data not available in label.

Warnings and precautions include diarrhea, hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, ocular toxicity, and pancreatic enzyme elevation. Dosage modifications are provided for each. For diarrhea: interrupt until recovery to Grade ≤1 for intolerable Grade 2 or Grade 3; resume at same or next lower dose; for recurrence, resume at next lower dose; permanently discontinue for Grade 4. For hepatotoxicity: interrupt until recovery for Grade 2, 3, or 4 ALT/AST without increased bilirubin or Grade 3 total bilirubin; resume at next lower dose; permanently discontinue for ALT or AST ≥3× ULN with total bilirubin ≥2× ULN or Grade 4 total bilirubin. For ILD/pneumonitis: permanently discontinue for any grade. For ocular toxicity: interrupt until recovery to Grade ≤1 for Grade 2; resume at next lower dose; for recurrence, permanently discontinue; permanently discontinue for Grade 3 or 4. For pancreatic enzyme elevation: interrupt until recovery to Grade ≤2 or baseline for Grade 3; resume at next lower dose; permanently discontinue for Grade 4. For other adverse reactions: interrupt until recovery to Grade ≤1 for intolerable or recurrent Grade 2 or Grade 3; resume at same or next lower dose; for recurrence, resume at next lower dose; permanently discontinue for Grade 4. Contraindications are not reported in the label.

Hyrnuo is approved for adult patients with locally advanced or metastatic non-squamous NSCLC with HER2 (ER