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

The US Food and Drug Administration has approved Thermo Fisher Scientific’s Ion Torrent Oncomine Dx Target Test as a companion diagnostic for identifying patients with HER2-mutated NSCLC who may be eligible for treatment with Bayer’s newly approved therapy, sevabertinib (HYRNUO). (Lab Manager)

Companion diagnostic • FDA approval • Non Small Cell Lung Cancer

Onco360 Has Been Selected as The National Specialty Pharmacy Partner for HYRNUO (sevabertinib) (GlobeNewswire) - "The Food and Drug Administration approved HYRNUO for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy."

Commercial • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer (FDA) - "FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in detecting HER2 (ERBB2) TKD activating mutations in patients with non-squamous NSCLC who may be eligible for treatment with sevabertinib....Efficacy was evaluated in patients with unresectable or metastatic, non-squamous NSCLC with HER2 (ERBB2) TKD activating mutations who had received prior systemic therapy and 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 • Companion diagnostic • FDA approval • Lung Non-Squamous Non-Small Cell Cancer • HER-2

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=370 | Active, not recruiting | Sponsor: Bayer | Trial primary completion date: Dec 2025 ➔ Nov 2026

First-in-human • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • 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" (DGHO 2025) - 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 • Pulmonary Disease • Solid Tumor • HER-2

Preclinical intracranial activity of NVL-330, a selective HER2 tyrosine kinase inhibitor (AACR-NCI-EORTC 2025) - "In this preclinical study, NVL-330 was broadly and selectively active against HER2 oncogenic alterations and demonstrated favorable brain penetrance and/or intracranial activity compared to T-DXd, zongertinib, and sevabertinib. This differentiated preclinical profile supports the potential for NVL-330 to address a medical need for patients with HER2-driven cancers, including those with brain metastases."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCB1 • EGFR • HER-2

Effect of Food and Esomeprazole on the Pharmacokinetics (PK) of BAY 2927088 (JADPRO 2025) - "These results support the administration of Serinexib with food or with acid-reducing agents in clinical trials. Serinexib was safe and well-tolerated in healthy participants."

PK/PD data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Obesity • Solid Tumor

Sevabertinib (BAY 2927088), a reversible HER2 inhibitor with activity in lung cancer (AACR-NCI-EORTC 2025) - "Sevabertinib is currently in phase 3 clinical trials. Notably, clinical responses have been reported in lung cancer patients with HER2 exon 20 insertions."

Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • NRG1

Recent Advances in the Development and Clinical Use of HER2 Inhibitors in Non-Small Cell Lung Cancer. (PubMed, Biomolecules) - "The first anti-HER2 inhibitor, trastuzumab-deruxtecan, was approved for previously treated advanced NSCLC with HER2 mutations, which accounts for 2-4% of NSCLC. The first anti-HER2 antibody, trastuzumab, was approved for HER2-positive metastatic breast cancer in 1998, and a combination therapy comprising trastuzumab, pertuzumab, and docetaxel demonstrated efficacy in the first-line setting...However, HER2-specific TKIs, such as zongertinib and BAY2927088, have demonstrated encouraging results...Despite different targets of HER2 mutations in NSCLC and HER2 amplification/overexpression in breast cancer, the development of HER2-targeting agents has been more advanced in breast cancer than in NSCLC. Therefore, pivotal clinical studies in breast cancer may help in identifying more effective therapies for NSCLC."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • 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

Molecular factors and ctDNA dynamics associated with clinical outcomes in patients with HER2-mutant NSCLC treated with sevabertinib (BAY 2927088): Exploratory analysis of the SOHO-01 study (ESMO 2025) - P1/2 | "Conclusions This exploratory analysis suggests that molecular features such as the presence of the HER2 YVMA variant, absence of TP53 co-alteration, early ctDNA clearance, are associated with favorable outcomes in patients with HER2-mutant NSCLC treated with sevabertinib. Associations between ctDNA dynamics and PFS, despite the limited follow-up information, align with previous findings in NSCLC cohorts treated with TKIs."

Circulating tumor DNA • Clinical • Clinical data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • TP53

Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer (Cancer Discov) - "we report the preclinical activity of sevabertinib in lung cancer models harboring alterations of HER2, including exon 20 insertions, point mutations, and amplification of wild-type ERBB2. We furthermore demonstrate the activity of sevabertinib in a cancer cell line dependent on a fusion of NRG1, a ligand for the HER2 family member and heterodimerization partner, HER3."

Preclinical • Non Small Cell Lung Cancer

Sevabertinib Monotherapy Elicits Durable Responses in HER2-Mutant NSCLC (Cancer Network) - "In cohort D (n = 81), which included patients who were previously treated, the objective response rate (ORR) by blinded independent central review (BICR) was 64% (95% CI, 53%-75%), with 2% achieving complete responses (CRs), 62% achieving partial responses (PRs), 25% having stable disease, 7% having progressive disease, and 4% not being evaluable. The disease control rate (DCR) was 81% (95% CI, 71%-89%)....In patients with non-squamous NSCLC and HER2 tyrosine kinase domain (TKD) mutations (n = 70), the ORR by BICR was 71%, and the median PFS was 9.6 months (95% CI, 6.9-14.7). In patients with HER2 Y772_A775dupYVMA alterations (n = 49), the ORR by BICR was 78%; in those with YVMA, the median PFS was 12.2 months (95% CI, 6.9-16.4), and in those with other TKD mutations, the median PFS was 7.0 months (95% CI, 4.0-not estimable [NE])."

P1/2 data • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • 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

Factors Associated With Clinical Outcomes in Patients With HER2-Mutant NSCLC Treated With Sevabertinib (BAY 2927088) (IASLC-WCLC 2025) - 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

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=20 | Recruiting | Sponsor: Bayer

New P1 trial • Hepatitis C • Hepatology • Liver Failure

Bayer’s sevabertinib (BAY 2927088) accepted for review in China (Bayer Press Release) - "Bayer...announced that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has accepted its new drug application (NDA) for the investigational compound sevabertinib (BAY 2927088), for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2/ERBB2) mutations and who have received a prior systemic therapy....The regulatory application for sevabertinib in China is based on positive results from the ongoing Phase I/II SOHO-01 trial in patients with advanced NSCLC harboring a HER2-activating mutation, with disease progression after ≥1 systemic therapies for advanced disease, and who were naïve to treatment with a HER2-targeted therapy or previously treated with HER2-targeted antibody-drug conjugates."

China filing • Non Small Cell Lung Cancer • Oncology

HER2 in Non-Small Cell Lung Cancer (NSCLC): Evolution of the Therapeutic Landscape and Emerging Drugs-A Long Way to the Top. (PubMed, Molecules) - "Despite numerous strengths, there is only one FDA/EMA-approved targeted therapy, an antibody-drug conjugate (ADC) called trastuzumab deruxtecan for pretreated patients with HER2 mutant NSCLC...But, two newly developed HER2-specific TKIs with low EGFR WT inhibition (BAY2927088 and zongertinib) reported encouraging results and received the breakthrough therapy designation from the FDA...A section of this paper is dedicated to the role of immunotherapy in HER2-altered NSCLC. The last section of this paper focuses on the drugs under development and their challenges."

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

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

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

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) granted FDA Priority Review for the treatment of patients with HER2-mutant non-small cell lung cancer (Bayer Press Release) - "Bayer today announced that the investigational compound sevabertinib (BAY 2927088) has been granted Priority Review status by the US Food and Drug Administration (FDA) for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2/ERBB2) mutations and who have received a prior systemic therapy....The regulatory application for sevabertinib is based on positive results from the ongoing Phase I/II SOHO-01 trial in patients with advanced NSCLC harboring a HER2-activating mutation, with disease progression after ≥1 systemic therapies for advanced disease, and who were naïve to treatment with a HER2-targeted TKI."

Evidence highlight • FDA filing • Priority review • Non Small Cell Lung Cancer • HER-2

Bayer Highlights New Data from Oncology and Women’s Health Portfolios at 2025 ASCO Annual Meeting (Bayer Press Release) - "In HER2-mutant non-small cell lung cancer (NSCLC), Bayer is presenting data from the ongoing SOHO-01 study, which is evaluating the safety and efficacy of sevabertinib (BAY 2927088) in patients with advanced HER2-mutant NSCLC who have been pretreated but naïve to HER2-targeted therapy or have not received any treatment for advanced disease."

P1/2 data • Non Small Cell Lung Cancer

BAY 2927088: a novel treatment option for patients with NSCLC with HER2 mutations (AACR 2025) - P1/2, P3 | "About 2-4% of patients with non-small cell lung cancer (NSCLC) carry either a HER2 exon20 insertion or a HER2 point mutation, which are potent oncogenic drivers.The antibody-drug conjugate fam-trastuzumab deruxtecan-nxki was the first targeted treatment option to be approved for patients with HER2-mutant NSCLC. We found that BAY 2927088 was also active in a subset of HER2-amplified breast and gastroesophageal cancer cell lines.Single-agent BAY 2927088 is currently being evaluated in clinical trials in patients with NSCLC with HER2 mutations. Preliminary results demonstrate efficacy and safety in pretreated patients (NCT05099172, NCT06452277)."

Clinical • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2