The FDA has granted accelerated approval to sevabertinib (Hyrnuo, Bayer Healthcare Pharmaceuticals Inc) for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor HER2 tyrosine kinase domain activating mutations and who have received prior systemic therapy.

The FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in detecting HER2 tyrosine kinase domain (TKD) activating mutations in patients who may be eligible for treatment with sevabertinib.

The oral tyrosine kinase HER2 inhibitor is the second one approved in the US for the indication, following the green light of zongertinib (Hernexeos, Boehringer Ingelheim Pharmaceuticals, Inc) in August. The antibody-drug conjugate trastuzumab deruxtecan (Enhertu) also carries a second-line indication for HER2-mutated NSCLC, among others.

Around 2%-4% of NSCLC patients carry HER2-activating mutations. Patients are predominantly women and sometimes younger with no smoking history. 

Approval was based on the single-arm, open-label SOHO-01 study of patients with locally advanced or metastatic HER2-mutated NSCLC, most of whom had a TKD mutation. All received sevabertinib 20 mg twice daily; the major efficacy outcomes were confirmed objective response rate (ORR) and duration of response, assessed by blinded independent central review.

Among 70 patients with a TKD mutation who had received prior systemic therapy but were naive to anti-HER2 therapy, the ORR was 71%, with a median duration of response of 9.2 months. Among 52 patients with a TKD mutation who had previously received HER2-targeted antibody drug conjugates (ADC), the ORR was 38%, with a median duration of response of 7 months.

By way of comparison, zongertinib’s label reports an ORR of 75% among 71 pretreated patients who were new to HER-2 targeted therapy, and 44% among those with previous anti-HER2 ADC exposure, both assessed by blinded independent central review. 

Duration of response to zongertinib was at least 6 months in 58% of the anti-HER2-naive arm, while median duration of response was 5.4 months in the prior-ADC group. 

In SOHO-01, diarrhea was the most common adverse event. The prescribing information includes warnings and precautions for diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity. 

Sevabertinib pricing was unavailable at press time, but the cost of thirty 60-mg tablets of rival zongertinib was $19,730.37 ($658 per tablet) before discounts, according to webmdrx.com. 

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com