Hyrnuo (sevabertinib) / Bayer, Broad Institute - LARVOL DELTA

CR19: SOHO-01: Safety and Efficacy of Sevabertinib in Patients with Advanced HER2-Mutant Non-Small Cell Lung Cancer (NSCLC) Who Were Pretreated but Naïve to HER2-Targeted Therapy or Had Not Received Any Treatment for Advanced Disease (HOPA 2026) - P1/2 | "Similar response rates were observed in patients with advanced HER2-mutant NSCLC who were pretreated but naïve to HER2-targeted therapy and in those treated in the first-line setting. Table"

Clinical • Metastases • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

CR09: Factors Associated with Clinical Outcomes in Patients with HER2-Mutant NSCLC Treated with Sevabertinib (BAY 2927088) (HOPA 2026) - P1/2 | "The findings underscore the importance of integrating clinical and molecular features to identify potential prognostic or predictive markers. As part of an ongoing study, these preliminary results emphasize the need for validation in a larger sample size to confirm these insights and further explore therapeutic strategies for patients with HER2-altered cancers."

Clinical • Clinical data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • HER-2 • TP53

310: Beyond EGFR and ALK: Updates in Biomarker-Driven Treatments in NSCLC (HOPA 2026) - "Emerging data on HER2-targeted therapies, trastuzumab deruxtecan, zongertinib, and sevabertinib in HER2 mutant NSCLC will also be reviewed, with emphasis on clinical efficacy, safety, and treatment sequencing. UAN: 0465-0000-26-058-L01-P Knowledge or Application Based: Application Learning Objectives: Describe the role of taletrectinib in the treatment of ROS1-rearranged NSCLCApply recently approved zenocutuzumab in the treatment of NSCLC with NRG1 fusionIntegrate telisotuzumab vedotin into therapeutic decisions for NSCLC patients with c-MET overexpressionReview clinical data evaluating the use of trastuzumab deruxtecan, zongertinib and sevabertinib in the treatment of HER2-mutation-positive NSCLC"

Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • MET • NRG1 • ROS1

SOHO-01: Safety and Efficacy of Sevabertinib in Patients With Advanced HER2 Mutation–Positive Non–Small Cell Lung Cancer Who Received Pretreatment but Were Naïve to HER2-Targeted Therapy or Had Not Received Any Treatment for Advanced Disease (HOPA 2026) - P1/2 | "Sevabertinib demonstrated manageable safety in both cohorts, which is consistent with previous reports. Diarrhea was the most common TRAE, but it was manageable and did not lead to treatment discontinuation. Similar response rates were observed in patients with advanced HER2 mutation–positive NSCLC who received pretreatment but were naïve to HER2-targeted therapy and in those who received treatment in the first-line setting."

Clinical • Metastases • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Factors Associated With Clinical Outcomes in Patients With HER2 Mutation–Positive NSCLC Who Received Sevabertinib (BAY 2927088) (HOPA 2026) - P1/2 | "This exploratory analysis of clinical and molecular factors in patients with HER2 mutation–positive NSCLC indicates favorable DOR and PFS among those who received only 1 previous line of therapy or who had specific molecular characteristics. The findings underscore the importance of integrating clinical and molecular features to identify potential prognostic or predictive markers. As part of an ongoing study, these preliminary results emphasize the need for validation in a larger sample size to confirm these insights and further explore therapeutic strategies for patients with HER2-altered cancers."

Clinical • Clinical data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • HER-2 • TP53

Mechanisms of zongertinib resistance in HER2-mutant non-small cell lung cancer and potential strategies to overcome resistance (AACR 2026) - "Consistent with our in vitro findings, tumors bearing C805S or S783C secondary mutations were resistant to zongertinib but sensitive to sevabertinib. Our findings identify novel HER2 mutations that mediate zongertinib resistance and indicate that sevabertinib may be effective against a subset of these genomic alterations."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • NRG1

Zongertinib-tolerant cells enhanced sensitivity to Topo1 inhibition in Her2-positive NCSLC (AACR 2026) - "For the treatment of Her2 mutated/amplified NSCLC, the antibody-drug conjugate Trastuzumab deruxtecan, several Her2-selective inhibitors, such as zongertinib and sevabertinib, have shown beneficial efficacy in clinical settings...Drug screening revealed that zongerR cells exhibited sensitivity to the multi-tyrosine kinase inhibitor ponatinib and foretinib. Additionally, PI3K/AKT pathway inhibitors (PI3Ki) such as GDC0941 and mTOR inhibitor PP242 also markedly suppressed the survival of zongerR cells in combination with zongertinib...Currently, zongertinib and T-Dxd have been approved for Her2-positive NSCLC, whereas treatment strategies to prolong the durable response have not been well-established. Further investigations were needed, but our findings suggested that T-DXd treatment after zongertinib may be a potential therapeutic strategy in a subset of Her2-positive NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer. (PubMed, N Engl J Med) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Sevabertinib: First Approval. (PubMed, Drugs) - "In November 2025, sevabertinib was approved under accelerated approval in the USA for use in adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumours have HER2 (ERBB2) TK domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. This article summarizes the milestones in the development of sevabertinib leading to this first approval for the treatment of locally advanced or metastatic NSCLC with HER2 (ERBB2) activating mutations."

Journal • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Zongertinib and Sevabertinib for Non-Squamous Non-Small Cell Lung Cancer (ASCO 2026) - No abstract available

Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer. (PubMed, N Engl J Med) - P1/2 | "Sevabertinib showed antitumor activity in patients with locally advanced or metastatic HER2-mutant NSCLC. Diarrhea was the most common adverse event. (Funded by Bayer; SOHO-01 ClinicalTrials.gov number, NCT05099172.)."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

SOHO-01: Safety and efficacy of BAY 2927088 in patients with advanced HER2-mutant non-small cell lung cancer (NSCLC) who were pretreated but naïve to HER2-targeted therapy or had not received any treatment for advanced disease. (ASCO 2025) - P1/2 | "BAY 2927088 demonstrated manageable safety in both cohorts, consistent with previous reports. Diarrhea was the most common TRAE, but it was manageable and did not lead to treatment discontinuation. Similar response rates were observed in patients with advanced HER2-mutant NSCLC who were pretreated but naïve to HER2-targeted therapy and in those treated in the first-line setting."

Clinical • Metastases • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): Results from the SOHO-01 study (ESMO 2025) - P1/2 | "Conclusions Sevabertinib showed rapid and durable responses with a manageable safety profile in pretreated and treatment-naïve pts with advanced HER2 -mutant NSCLC. These data support sevabertinib as a potential practice-changing, new targeted therapy for pts with HER2 -mutant NSCLC."

Late-breaking abstract • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • HER-2

Phase I/II SOHO-01 study of sevabertinib (BAY 2927088) in HER2-mutant non-small cell lung cancer (NSCLC): Safety and efficacy in Asian patients (ESMO Asia 2025) - P1/2 | "Durable responses were observed in Asian patients with advanced NSCLC with HER2-activating mutations treated with sevabertinib. Safety was manageable and consistent with previous reports."

Clinical • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Characterization and management of sevabertinib-induced diarrhea in the SOHO-01 study (ELCC 2026) - P1/2 | "Timing of the last dose of anti-PD(L)-1 therapy or platinum-based chemotherapy was a potential predictor of G3 diarrhea.Conclusions Despite the high incidence of any-G and G3 diarrhea, events were short and effectively managed without compromising sevabertinib efficacy. This longitudinal, exploratory assessment provides clinically relevant context beyond conventional AE reporting and insights into strategies for managing diarrhea in pts treated with sevabertinib."

Lung Cancer • Non Small Cell Lung Cancer

HER2 Alterations in Non-Small Cell Lung Cancer: Emerging Perspectives on the Therapeutic Landscape. (PubMed, Int J Mol Sci) - "In the past few years, targeted therapeutic modalities such as antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (the first agent to be granted FDA approval for HER2-mutant NSCLC), alongside selective tyrosine kinase inhibitors (TKIs), including zongertinib and sevabertinib, have demonstrated robust systemic efficacy and notable intracranial penetration. This comprehensive review delineates the molecular landscape and clinical phenotypes of HER2-altered NSCLC, synthesizes interim and mature data from ongoing clinical trials evaluating anti-HER2 therapies, and critically examines efficacy and safety results from different classes of targeted agents. Further research is crucial to uncover potential mechanisms of resistance in NSCLC with HER2 mutations and define sequencing or combinatorial strategies pertinent to optimizing individualized patient management."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Phase I/II SOHO-01 study of BAY 2927088 in patients with previously treated HER2-mutant NSCLC: Safety and efficacy results from 2 expansion cohorts (ELCC 2025) - P1/2 | "Median age was 62.0 years (D) and 62.5 years (E), 63.6% (D) and 61.8% (E) of pts were female, 70.5% (D) and 64.7% (E) had never smoked, 54.5% (D) and 76.5% (E) had received ≥2 therapy lines, and 82.4% (E) had received trastuzumab deruxtecan. The safety profile of BAY 2927088was manageable across cohorts. Treatment with BAY 2927088 led to durable responses in pts naïve to HER2-targeted therapy and in those who had received a HER2-targeted ADC."

Clinical • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

BUDGET IMPACT OF SEVABERTINIB FOR HER2-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SQUAMOUS NSCLC WITH PRIOR SYSTEMIC THERAPY FROM A UNITED STATES PAYER PERSPECTIVE (ISPOR 2026) - "Treatment comparators included zongertinib and fam-trastuzumab deruxtecan-nxki. Sevabertinib as a treatment option for HER2-mutant NSCLC is associated with minimal budget impact for US payers, due to lower administration and AE costs as cost offsets, which supports its inclusion on formularies."

HEOR • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • HER-2

Different Lung Cancer–Associated ERBB2 Variants Exhibit Distinct Therapeutic Vulnerabilities (IASLC-TTLC 2026) - "Our study reveals that the specific ERBB2 mutation subtype is functionally relevant for determining the sensitivity profile to T-DXd and the novel ERBB2 TKIs zongertinib and sevabertinib. These findings have implications for understanding the biology of ERBB2-mutant NSCLC and for optimizing treatment strategies for patients with this disease."

Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2 • KRAS • PIK3CA • TMB

Acquired ERBB2 Amplification and Overexpression as On-Target Resistance Mechanisms to Zongertinib With Subsequent Response to Trastuzumab-Deruxtecan: A Case Report. (PubMed, JTO Clin Res Rep) - "A number of drugs are in development for the treatment of ERBB2(HER2)-mutated NSCLC, including antibody-drug conjugates such as trastuzumab-deruxtecan and tyrosine kinase inhibitors such as zongertinib and sevabertinib. Herein, we report a case of relapsed advanced ERBB2-mutant NSCLC with acquired resistance to zongertinib potentially mediated through ERBB2 amplification and HER2 3+ immunohistochemistry overexpression with subsequent durable response to fifth-line trastuzumab-deruxtecan. We propose this as a mechanism for zongertinib resistance, one that may underpin a biological rationale for future ERBB2 tyrosine kinase inhibitor-antibody-drug conjugate combination therapy."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

THE BUDGET IMPACT OF INTRODUCING ZONGERTINIB INTO THE FORMULARY FOR TREATMENT-NAÏVE AND PRETREATED HER2-MUTANT ADVANCED NSCLC IN THE UNITED STATES (ISPOR 2026) - "The introduction of zongertinib into the formulary for treatment-naïve and previously treated patients with HER2-mutant advanced NSCLC is associated with a limited budgetary impact in the US."

HEOR • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • HER-2

Hyrnuo: Expiry of patents related to active ingredients in Germany, France, Italy, Switzerland, Spain, UK, China, Japan, Brazil, Canada and US in 2040 (Bayer AG) - Annual Report 2025

Patent • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A Study Evaluating How Moderate Liver Impairment Affects the Absorption, Distribution, Metabolism, and Elimination of Sevabertinib After a Single Oral Dose (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Bayer | Recruiting ➔ Completed

Trial completion • Hepatitis C • Hepatology • Liver Failure

SOHO-02: Phase III trial of BAY 2927088 in patients with locally advanced or metastatic NSCLC with HER2-activating mutations. (ASCO 2025) - P3 | "Overall, 278 eligible patients will be randomized to BAY 2927088 p.o. 20 mg twice daily or standard of care (SoC; pembrolizumab in combination with cisplatin/pemetrexed or carboplatin/pemetrexed) in 21-day cycles. Impact of BAY 2927088 on patient health-related quality of life and symptom severity will be evaluated using EORTC QLQ-C30 and NSCLC-SAQ. Enrollment is ongoing."

Clinical • Metastases • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2