ESMO: Boehringer, Bayer seek first-line HER2+ NSCLC role

Fresh from a return to oncology with the FDA approval of Hernexeos as a treatment for HER2-positive non-small cell lung cancer (NSCLC), Boehringer Ingelheim is racing to expand its label, with Bayer in hot pursuit.

At ESMO, both companies reported new clinical trial data for their drugs as first-line options for this type of lung cancer. Boehringer had new data from the phase 1b Beamion LUNG-1 study, which underpinned the approval of Hernexeos (zongertinib) as a second-line therapy, while the phase 1/2 SOHO-01 study of Bayer's sevabertinib (BAY 2927088) rival was also presented. Both drugs are orally active HER2 tyrosine kinase inhibitors.

According to Boehringer, Hernexeos achieved a 77% objective response rate (OOR) in a cohort of previously untreated HER2+ NSCLC patients in Beamion Lung-1, with 8% complete responses and 69% partial responses. The disease control rate – including patients whose tumours stabilised, but did not shrink – came in at 96%.

The result is roughly in line with the earlier readout from the study in patients treated second-line with Boehringer's drug, boding well for a positive outcome when the company files for approval to expand its label. Hernexeos already has a breakthrough designation from the FDA for the first-line setting.

In SOHO-1, sevabertinib achieved an ORR of 71% in previously untreated patients, 38% in a cohort who received the drug second-line after HER2-directed antibody-drug conjugate (ADC) therapy, and 64% in patients treated with other drugs first-line.

HER2 mutations are seen in between 2% and 4% of NSCLC cases, and are associated with a poor prognosis and a higher incidence of the cancer spreading to the brain. Patients with HER2-mutant NSCLC are predominantly women, and tend to be younger and non-smokers.

Platinum-based chemotherapy and, in some cases, immunotherapy are standard first-line treatments, but the hope is that these targeted therapies can improve outcomes and minimise toxicity.

Both oral HER2 inhibitors were fairly well tolerated as first-line therapies, with discontinuation rates due to toxicity of 9% for Hernexeos and 3% with sevabertinib, although diarrhoea was an issue with both drugs.

Bayer has now filed sevabertinib for approval in the second-line setting in the US and China, on the back of other cohorts in SOHO-1, setting up approvals next year.

Neither Boehringer nor Bayer has given a timeline for filing for use in the previously untreated population, and both are also running phase 3 trials – respectively, Beamion LUNG 2 and SOHO-2 – that are recruiting frontline HER2+ NSCLC patients.

Boehringer is also running the Beamion LUNG-3 of trial Henexeos as adjuvant monotherapy for early-stage HER2+ NSCLC, while Bayer's panSOHO study is focusing on advanced, non-NSCLC solid tumours expressing HER2.