FDA Approves Boehringer's Hernexeos as First-Line Treatment for HER2-Mutant Lung Cancer

The FDA on February 26 granted accelerated approval to Boehringer Ingelheim's Hernexeos (zongertinib) for adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain activating mutations, extending the drug to patients who have not received prior therapy, the agency announced. It was the second approval under the Commissioner's National Priority Voucher pilot program, with a decision 44 days after the application was filed on January 13.

Hernexeos, an oral tyrosine kinase inhibitor that targets HER2, received accelerated approval in August 2025 for patients with these mutations who had already received systemic therapy. The FDA said the new decision extends that option to patients who have not been treated.

Data behind the approval

The approval is based on a cohort of 72 previously untreated patients in Beamion LUNG-1, a single-arm, open-label, multicenter Phase 1b trial, according to the February 2026 prescribing information. The objective response rate was 76%, with 11% complete and 65% partial responses, Boehringer said in its announcement, distributed via the PharmaShots newswire. Responses lasted at least six months in 64% of responders, and Targeted Oncology reported that 44% of responders kept a response for 12 months or longer.

The FDA said that in the trial data submitted, 76% of previously untreated patients had a substantial decrease in tumor size, compared with 30% to 45% typically expected with current standard care.

Because the approval is accelerated and based on response rate and duration of response, continued approval may depend on confirming clinical benefit in a confirmatory trial. Boehringer said it is enrolling patients in Beamion LUNG-2, a Phase 3 trial of zongertinib as a first-line treatment.

"Now these patients finally have a targeted treatment option that they can receive immediately following identification of a HER2 mutation," said John Heymach of the University of Texas MD Anderson Cancer Center, the coordinating investigator for Beamion LUNG-1, in the company's release.

Voucher review and safety

The FDA said it proactively granted Hernexeos a national priority voucher on November 6, 2025, based on preliminary data. The pilot program gives selected companies enhanced communication and rolling review to shorten review times. "In this case a final decision was rendered 44 days after the filing date," FDA Commissioner Marty Makary said. The drug also holds Breakthrough Therapy and Priority Review designations.

Serious side effects listed by the FDA include hepatotoxicity, left ventricular dysfunction, interstitial lung disease or pneumonitis, and embryofetal toxicity. The most common side effects are diarrhea, rash, hepatotoxicity, fatigue, nausea, musculoskeletal pain and upper respiratory tract infection. Targeted Oncology reported that the recommended dose is 120 mg once daily for patients under 90 kg and 180 mg for those at or above it.

Patients are selected with an FDA-authorized test for the HER2 mutations, the label says.