sevabertinib (BAY 2927088) / Bayer, Broad Institute - LARVOL DELTA

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

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

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

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: A Study to Learn More About How Well BAY 2927088 Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations in the Genes of Human Epidermal Growth Factor Receptor 2 (HER2) (clinicaltrials.gov) - P3 | N=278 | Recruiting | Sponsor: Bayer | Trial completion date: May 2028 ➔ Apr 2029

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Bayer starts Phase II clinical study with BAY 2927088 in metastatic or unresectable HER2 mutant solid tumors (Bayer Press Release) - "Bayer announced today that the first patient has been enrolled in the global Phase II panSOHO study, an open-label clinical trial, assessing the efficacy and safety of investigational agent BAY 2927088 in adult patients with metastatic or unresectable solid tumors harboring HER2-activating mutations. These include tumors of the colon or rectum, the uterus and the cervix, the bladder, and the biliary tract (includes gall bladder and bile ducts) as well as other types of solid tumors, excluding advanced non-small cell lung cancer (NSCLC)."

Trial status • Biliary Tract Cancer • Bladder Cancer • Cervical Cancer • Colorectal Cancer • Gallbladder Cancer • Uterine Cancer

Safety and Efficacy of BAY 2927088 In Patients with HER2 -Mutant NSCLC: Expansion Cohort from the SOHO-01 Study (JSMO 2025) - No abstract available

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

panSOHO: A Study to Learn More About How Well Treatment With BAY2927088 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 | Not yet recruiting ➔ Recruiting

Enrollment open • Pan tumor • Oncology • Solid Tumor

SOHO-02: A Study to Learn More About How Well BAY 2927088 Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations in the Genes of Human Epidermal Growth Factor Receptor 2 (HER2) (clinicaltrials.gov) - P3 | N=278 | Recruiting | Sponsor: Bayer | Trial primary completion date: Jun 2026 ➔ Apr 2027

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

panSOHO: A Study to Learn More About How Well Treatment with BAY2927088 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 | Not yet recruiting | Sponsor: Bayer

New P2 trial • Oncology • Solid Tumor

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 | Recruiting ➔ Active, not recruiting

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

Expanded Access to Provide BAY2927088 for the Treatment of Locally Advanced or Metastatic NSCLC With HER2 Mutation (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Bayer

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

BEAMING-Lung01 updated: Zongertinib 120 mg a potential treatment approach in HER2-mutant NSCLC Challenges 🙉 in HER2-m: -Brain activity with TKI, -1st L: ADCs vs TKI, ADC vs CT, Chemo + TKI vs TKI/ADC? 😵‍💫🤯 -Zongertinib vs BAY292708 (ORR 72% PFS 7,5mo.) -ImmunoTx #ESMOASIA24

New Hope for Patients With HER2-Mutant NSCLC: Durable Responses to Two Novel Targeted Therapies (THE ASCO POST) - "'BAY 2927088 treatment led to rapid and durable responses in patients with previously treated HER2-mutant NSCLC,' lead study author Xiuning Le, MD, PhD...said during the presentation."

Media quote

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 (CSCO 2024) - "Study Group: [Organizing Committee]"

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

Emerging Therapies in HER2-Mutant NSCLC: Expert Insights From Dr John Heymach (AJMC) - "Following his HER2 presentation, John Heymach, MD, PhD...discussed current advancements in this field, important considerations for patient selection, the safety and tolerability of HER2-targeting therapies, future research efforts, and more."

A randomized phase III trial evaluating oral BAY 2927088, compared with standard of care, as first-line treatment of locally advanced or metastatic NSCLC harboring HER2-activating mutations (SOHO-02) (ESMO 2024) - "278 eligible pts will be randomized to oral BAY 2927088 (20 mg twice daily) or standard of care (SoC; pembrolizumab in combination with platinum-based chemotherapy [cisplatin or carboplatin] and pemetrexed) administered in 21-day cycles. Health-related quality of life and symptomatic side effects will be measured using the EORTC QLQ-C30, NSCLC-SAQ, and EQ-5D-5L, including VAS. First patient, first visit is in June 2024."

Clinical • Metastases • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell 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 (IASLC-WCLC 2024) - "Overall, 278 eligible patients will be randomized to oral BAY 2927088 (20 mg twice daily) or standard of care (SoC; pembrolizumab in combination with platinum-based chemotherapy [cisplatin or carboplatin] and pemetrexed) administered in 21-day cycles. Patients’ health-related quality of life and symptomatic side effects will be measured using the EORTC QLQ-C30, NSCLC-SAQ, and EQ-5D-5L, including VAS. 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

PC03. Press Conference (IASLC-WCLC 2024) - "These sessions are open only to registered media who have been credentialed to cover the meeting. PL04.13 - Aumonertinib Maintenance after Chemoradiotherapy in stage III Non-Small-Cell Lung Cancer: Interim Results of the phase III study (POLESTAR PL04.10 - Osimertinib with or without savolitinib as 1L in de novo MET aberrant, EGFRm advanced NSCLC (CTONG 2008): A Phase II trial PL04.07 - FURTHER: A Global, Randomized Study Evaluating Firmonertinib At Two Dose Levels in EGFR TKI-Naive, Advanced NSCLC with EGFR PACC Mutations PL04.03 - Safety and Efficacy of BAY 2927088 in Patients With HER2-Mutant NSCLC: Expansion Cohorts from the Phase I/II SOHO-01 Study PL04.04 - Primary Phase Ib Analysis of Beamion LUNG-1: Zongertinib (BI 1810631) in Patients with HER2 Mutation-Positive NSCLC"

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

Dr Le on SOHO-01 Data With BAY 2927088 in HER2-Mutated NSCLC (OncLive) - "Xiuning Le, MD, PhD, discusses updated findings from the phase 1/2 SOHO-01 trial."

Video

SOHO-01: BAY 2927088, a novel TKI, in HER2-mutant NSCLC (YouTube) - "Xiuning Le, MD, PhD...discusses updated findings from the SOHO-01 study (NCT05099172) of BAY 2927088, a reversible tyrosine kinase inhibitor (TKI), in patients with HER2-mutant non-small cell lung cancer (NSCLC) naïve to HER2-targeted therapy. With a median follow-up of 10.9 months, BAY 2927088 demonstrated a durable and early response rate. The treatment was well-tolerated, with diarrhea being the most common adverse event. This interview took place at the 2024 World Conference on Lung Cancer (WCLC) in San Diego, CA."

Interview • Video

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