Targeted anticancer agents for HER2 lung cancer show results

Asia clinical trials

Bayer and Boehringer Ingelheim unveil their clinical trial data…major indicators have been improved

Oral TKI effectiveness have been confirmed…"A positive assessment for expanded treatment option"

Results from new drugs for HER2-mutated lung cancer were presented at the ESMO ASIA 2025, which kicked off on December 5 in Singapore

New drugs for HER2-mutated Non-Small Cell Lung Cancer (NSCLC) have shown effectiveness in Asian patients.

Bayer and Boehringer Ingelheim have officially joined the competitive landscape by releasing their Asian clinical data for 'Hyrnuo (sevabertinib)' and 'Hernexeos (zongertinib)', respectively.

Following the existing therapy, Enhertu, these new treatment options have all demonstrated consistent antitumor effects and predictable safety profiles in Asian patients, signaling an important turning point in changing the treatment strategy for HER2-mutated lung cancer.

At ESMO Asia 2025 in Singapore on December 5, Bayer released Asian patient data for its oral HER2-targeted therapy, Hyrnuo, which recently secured U.S. FDA approval. 

The analysis presented was an interim result focused on 140 Asian patients who participated in Cohorts D, E, and F of the pivotal SOHO-01 study.

The study showed that Hyrnuo demonstrated consistent efficacy in both treatment-experienced patients (D) and patients undergoing first-line treatment (F).

Specifically, the objective response rate (ORR) reached 66.7% in the first-line cohort (F) and 61.4% in Cohort D (patients previously treated but HER2 TKI-naïve). 

A response rate of 46.9% was also confirmed in Cohort E, which had prior HER2 ADC experience, indicating a significant antitumor effect regardless of prior treatment type. 

The duration of response (DOR) was 12.6 months in Cohort D and 8.5 months in Cohort E. The first-line cohort (F) showed sustained responses lasting at least 8 months, although accurate median calculation was difficult due to data censoring.

The characteristics of the Asian patients were distinct. 70–86% were non-smokers, and over 60% were female, consistent with the frequently reported East Asian characteristics of HER2-mutated lung cancer. The mean age ranged from 59 to 66 years, reflecting the patient population observed in clinical practice.

Safety analysis showed a predictable HER-family TKI profile. Treatment-related adverse events (TRAEs) were reported in 99.3%, but most (68.6%) were Grade 1–2. The most common AE was diarrhea (76.4%), with Grade 3 occurring in 11.4%. Dose reduction occurred in 27.1%, and discontinuation in 3.6%. Notably, no cases of Interstitial Lung Disease (ILD), a serious concern with HER2-targeted agents, were reported, highlighting Hyrnuo's strength in a safety profile.

Professor Daniel Shao Weng Tan of the National Cancer Centre Singapore 

HER2-mutated lung cancer is a rare cancer, accounting for only 2–4% of all NSCLC, but the entry of new drugs like Hyrnuo and Enhertu is rapidly heating global competition. Hyrnuo's Asian data, which simultaneously demonstrating first-line potential, consistent response rates regardless of prior therapy, and manageable safety, suggests the emergence of another critical axis in the shifting treatment strategy for HER2-mutated lung cancer.

Professor Daniel Shao Weng Tan of the National Cancer Centre Singapore stated during presentation, "The durable response and predictable safety confirmed in Asian patients support Hyrnuo's potential as a treatment option," and emphasized, "This drug could contribute to broadening the choices available to HER2-mutated lung cancer patients."

Boehringer Ingelheim’s Hernexeos (zongertinib) achieves over 70% ORR in Asian patients

Following Hyernuo, Boehringer Ingelheim’s HER2-targeted therapy Hernexeos also demonstrated a powerful therapeutic effect in Asian patients, further intensifying competition in the HER2-mutated lung cancer market.

Hernexeos is designed to selectively inhibit HER2 while not targeting wild-type EGFR, minimizing the toxicity issues seen with prior HER-family treatments. This drug has already received U.S. FDA approval and has been designated as an Innovative New Drug in China, recognizing its accelerated development pathway.

This ESMO Asia featured results from the Asian subgroup analysis of Cohort 1 of the global Phase 1b Beamion LUNG-1 study, targeting HER2-mutated NSCLC patients who had received prior systemic chemotherapy.

Hernexeos was confirmed at a single dose of 120 mg once daily following an interim analysis. Efficacy endpoints, including ORR, DOR, and progression-free survival (PFS), were assessed based on Blinded Independent Central Review (BICR).

Of the total 75 patients in the global cohort, 39 were East Asian (18 from China, 12 from Korea, and 9 from Japan). The analysis showed that the ORR for all East Asian patients was 76.9%, and the disease control rate (DCR) was 100%. 

The median DOR for the East Asian cohort was 14.1 months, and the median PFS was 15.5 months, suggesting stable and long-term efficacy is possible even in previously treated HER2-mutated patients.

Professor Yi-Long Wu of the Department of Oncology at Guangdong Lung Cancer Institute

Notably, the Chinese patient subgroup showed an even higher response rate, with an ORR of 83.3% and a DCR of 100%. A DOR of 14.1 months was observed in some Chinese patients, and PFS was 15.5 months, consistent with the overall East Asian cohort. Considering that therapeutic response to HER2-mutated lung cancer can be sensitive to ethnic or regional differences, these results are interpreted as clear evidence of Hernexeos's competitiveness in Asian patients.

Safety was also manageable. Adverse drug reactions were reported in 92% of all Asian patients, with moderate or greater severity (≥ Grade 3) occurring in 18%. The most common AE was diarrhea (38%), which was mostly Grade 1 and manageable. Critically, no cases of drug-related ILD, a significant concern with HER2-family drugs, were reported, supporting Hernexeos's safety advantage.

The investigators stated, "Hernexeos's mechanism certainty and clinical value were already recognized through the publication of global data in the New England Journal of Medicine, and this Asian data shows a consistent trend with those results," and emphasized, "The strong response rate, durability lasting over one year, low discontinuation rate, and predictable safety profile increase the likelihood that Hernexeos will become an important targeted therapy for HER2-mutated NSCLC."