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

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

panSOHO: A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2) (clinicaltrials.gov) - P2 | N=111 | Recruiting | Sponsor: Bayer | Trial completion date: Oct 2027 ➔ Oct 2029 | Trial primary completion date: Feb 2027 ➔ Feb 2029

Trial completion date • Trial primary completion date • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Lung Cancer • Oncology • Solid Tumor • HER-2

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs in Japan; sevabertinib for lung cancer, gemcitabine intravesical system and durvalumab for bladder cancer, azacitidine for leukemia, cemiplimab for skin cancer, and ropeginterferon alfa-2b for essential thrombocythemia. (PubMed, Int J Clin Oncol) - No abstract available

Japanese regulatory • Journal • Bladder Cancer • Essential Thrombocythemia • Genetic Disorders • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Leukemia • Lung Cancer • Myeloproliferative Neoplasm • Oncology • Skin Cancer • Solid Tumor • Thrombocytosis

Safety and anti-tumor activity of BAY 2927088 in patients with HER2-mutant NSCLC: Results from an expansion cohort of the SOHO-01 phase I/II study. (ASCO 2024) - P1/2 | "BAY 2927088 led to rapid, substantial, and durable responses in pts with pretreated HER2-mutant NSCLC. The safety profile was consistent with previously reported data. These data support the further clinical development of BAY 2927088 in pts with HER2-mutant NSCLC."

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

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

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

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

Intracranial Outcomes and Treatment Response in HER2 (ERBB2)-Mutated Non-Small Cell Lung Cancer With Brain Metastases (IASLC-WCLC 2026) - "The median time to intracranial progression for patients who had active progressive brain metastases prior to the start of a given therapy was 7.4 months for pemetrexed-based regimens, 3.2 months for trastuzumab deruxtecan (T-DXd), and 1.6 months for other HER2 targeted therapies (eg, trastuzumab, TDM-1, afatinib)...Conclusions : Pemetrexed-based therapies and T-DXd each achieved only modest CNS disease control in this cohort, and intracranial progression as well as development of LMD were common in patients with existing brain metastases, despite most patients receiving radiation as well. Therapies with better CNS activity for HER2-mutated NSCLC are therefore needed, potentially with newly-approved tyrosine kinase inhibitors such as zongertinib and sevabertinib."

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

On-Target Acquired Resistance to Zongertinib and Strategy to Overcome It - in Vitro Study usingHER2ex20 Insertion Models (IASLC-WCLC 2026) - "Methods : We examined efficacy of zongertinib, sevabertinib and other TKIs with HER2 inhibitory activity (erlotinib, afatinib, poziotinib, mobocertinib, and osimertinib) using murine pro-B-cell line (Ba/F3) models harboring one of three most common HER2 exon 20 insertions (A775_G776insYVMA (YVMA), G776delinsVC (VC) and P780_Y781insGSP (GSP)). Conclusions : These findings indicate that distinct compound mutations confer differential resistance to HER2-TKIs depending on the original HER2 exon 20 insertion. Zongertinib-resistant mutations, such as YVMA+S783A and GSP+G776C, remained sensitive to poziotinib, whereas compound mutations associated with poziotinib resistance, including YVMA+C805S and VC+C805S, were effectively inhibited by sevabertinib."

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

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

panSOHO: Phase II trial of BAY 2927088 in patients with unresectable or metastatic solid tumors other than NSCLC with HER2‑activating mutations. (ASCO 2025) - P2 | "Impact of BAY 2927088 on patient quality of life will be evaluated by EORTC QLQ-C30. Enrollment is open."

Clinical • Metastases • P2 data • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Molecular Landscape of Acquired Resistance to Sevabertinib in HER2-mutant NSCLC: Exploratory Biomarker Analysis of SOHO-01 (IASLC-WCLC 2026) - P1/2 | "Clinically, patients harboring secondary HER2 T862A mutations exhibited comparable duration of response and time to progression compared with those without. Preclinical and structural modeling studies are underway to elucidate the biological impact of the HER2 T862A alterations on sevabertinib binding and activity."

Biomarker • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • HER-2 • PIK3CA • TP53

SOHO-01: Updated efficacy and safety of sevabertinib in advanced HER2-mutant NSCLC, including first-line patients (pts) and those with active brain metastases (ESMO 2026) - No abstract available

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

Acquired Resistance to Zongertinib in Patients With HER2Mutant Advanced Non-Small Cell Lung Cancer (IASLC-WCLC 2026) - "Introduction : Zongertinib, an irreversible HER2-selective tyrosine kinase inhibitor (TKI), has shown transformative efficacy in HER2-mutant non-small-cell lung cancer (NSCLC). The HER2 C805S mutation defines a distinct structural mechanism of therapeutic escape, for which sevabertinib and T-DXd represent rational salvage strategies. $$graphic_4E1AFEA6-6E73-4793-B424-27A121AFA9AB$$ $$graphic_3DE555C8-7179-4680-BFCA-A269ABEB97CD$$"

Clinical • Metastases • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCDC6 • MTAP • PIK3CA

Clinical Characteristics, Genomic Subtypes, and Outcomes of HER2-Altered NSCLC: A Multicenter Real-World Study in Taiwan (IASLC-WCLC 2026) - "The use of antibody-drug conjugates (ADCs) was associated with improved OS (aHR 0.50; p<0.001), whereas TKIs for HER2 alterations (including afatinib, zongertinib, and BAY 2927088) were not. TP53 co-mutation identifies a clinically relevant high-risk subgroup, while the use of ADCs is associated with improved survival outcomes. These findings support integrated clinicogenomic risk stratification in clinical practice and provide a framework for designing prospective biomarker-driven trials to further optimize treatment sequencing and personalize therapeutic decision-making in HER2-altered NSCLC."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Respiratory Diseases • Solid Tumor • HER-2 • TP53

Early evidence of efficacy in patients (pts) with non-small cell lung cancer (NSCLC) with HER2 exon20 insertion (ex20ins) mutations treated in a phase I study with BAY 2927088 (ESMO 2023) - P1 | "In pts with HER2 ex20ins mutant disease, BAY 2927088 showed encouraging preliminary anti-tumour activity. These results warrant further investigation of BAY 2927088 in pts with NSCLC."

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

FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non-small cell lung cancer (FDA) - "Efficacy was evaluated in patients with locally advanced or metastatic, non-squamous NSCLC with HER2 (ERBB2) TKD activating mutations who received sevabertinib in SOHO-01 (NCT05099172), an open-label, single-arm, multicenter, multi-cohort clinical trial. HER2 (ERBB2) activating mutations were determined in tumor tissue or plasma by local laboratories prior to enrollment."

Accelerated approval • FDA approval • Project Orbis • Lung Non-Squamous Non-Small Cell Cancer

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

Acquired Resistance to Zongertinib in Patients With HER2Mutant Advanced Non-Small Cell Lung Cancer (IASLC-WCLC 2026) - "Conclusions : Acquired resistance to zongertinib involves diverse genomic and histologic adaptations. The HER2 C805S mutation defines a distinct structural mechanism of therapeutic escape, for which sevabertinib and T-DXd represent rational salvage strategies."

Clinical • Metastases • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCDC6 • MTAP • PIK3CA

Efficacy and Safety of TKI Versus ADC in Advanced or Metastatic HER2 Mutant Non-Small Cell Lung Cancer: A Metanalysis (IASLC-WCLC 2026) - "Notably, newer selective TKIs such as Zongertinib (ORR 71%) and Sevabertinib (ORR 64%) demonstrated superior efficacy compared to older pan-HER TKIs, such as Poziotinib (ORR 28-39%) and Pyrotinib (ORR 30%). However, ADCs were associated with a higher incidence of ILD/pneumonitis, whereas TKIs were more likely to cause diarrhea. These findings support the potential of newer HER2-specific TKIs as promising therapeutic options for HER2-mutant NSCLC, with an improved safety profile and efficacy."

ADC • Clinical • Metastases • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Safety and Efficacy of BAY 2927088 In Patients with HER2-Mutant NSCLC: Expansion Cohort from the Phase I/II SOHO-01 Study (IASLC-WCLC 2024) - P1/2 | "Treatment with BAY 2927088 led to rapid, substantial, and durable responses in patients with heavily pretreated HER2 -mutant NSCLC. The safety profile of BAY 2927088 was manageable and consistent with previous reports. These data support the ongoing investigation of BAY 2927088 in patients with advanced NSCLC harboring HER2 mutations."

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

Independent CE Dinner Satellite Symposium: Empowering Oncology Teams in HER2 Testing: Applying the New NCCN Standards to Transform NSCLC Care (JADPRO 2026) - "4) Evaluate treatment pathways for HER2-altered NSCLC, including agents such as T-DXd, sevabertinib, and zongertinib and their indications. 6) Enhance communication across multidisciplinary teams to ensure complete testing orders, accurate interpretation, and timely patient navigation. 7) Describe the toxicity profiles of newer HER2-targeted therapies, including T-DXd and other emerging HER2-directed agents, and apply evidence-based strategies for early recognition, monitoring, supportive care, and management of treatment-related adverse events to improve patient safety and clinical outcomes"

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

Bayer’s sevabertinib approved in Japan for patients with HER2-mutant non-small cell lung cancer (Bayer Press Release) - "The MHLW approval is supported by data from the global Phase I/II SOHO-01 trial (NCT05099172)."

Japan approval • Non Small Cell Lung Cancer

SOHO-01: First in Human Study of BAY2927088 in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations in the Genes of Epidermal Growth Factor Receptor (EGFR) and/or Human Epidermal Growth Factor Receptor 2 (HER2) (clinicaltrials.gov) - P1/2 | N=400 | Recruiting | Sponsor: Bayer | Trial completion date: Jun 2029 ➔ Jun 2031

First-in-human • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

Phase 1 Study in Healthy Adults to See How Sevabertinib Changes Metformin Levels in the Body (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Bayer

New P1 trial