The FDA has granted priority review designation to sevabertinib for the first-line treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain (TKD)–activating mutations.1
The application was granted priority review status based on data from cohort F of the phase 1/2 SOHO-01 trial (NCT05099172). In treatment-naive patients (n = 73), the objective response rate (ORR) and median duration of response (DOR) were 71% (95% CI, 59%-81%) and 11.0 months (95% CI, 8.1-not estimable [NE]).2 The median progression-free survival was NE (95% CI, 9.6-NE) and the disease control rate was 89% (95% CI, 80%-95%).
Best overall responses included a complete response in 3 patients (4%), a partial response in 49 (67%), stable disease in 16 (22%), and progressive disease in 2 (3%). One patient was not evaluable and another 2 were not available for assessment.
“The FDA’s priority review decision for sevabertinib is an important milestone that underscores Bayer’s commitment to precision oncology, addressing critical unmet needs in patients with HER2‑mutant NSCLC,” Christian Rommel, PhD, head of research and development at Bayer’s Pharmaceuticals Division, said in a news release.1 “Patients with HER2-mutant NSCLC currently have limited treatment options, and there is an urgent need for more effective and better tolerated therapies that can be used early in the disease course to help improve survival outcomes.”
Key Findings From Cohort F of SOHO-01
- Among 73 first-line patients, sevabertinib achieved an ORR of 71% (95% CI, 59%-81%) and a disease control rate of 89%, with best overall responses including complete response in 4% and partial response in 67% of patients.
- The median DOR was 11.0 months (95% CI, 8.1-NE) and the median PFS had not been reached (95% CI, 9.6-NE).
- The most common treatment-related AEs were diarrhea (84%), rash (51%), and stomatitis (26%), with the majority being low grade (grade 1-2, 74%), though grade 3-5 events occurred in approximately 23% of patients.
How was the SOHO-01 trial designed, and who was eligible for enrollment?
SOHO-01 is an open-label, single-arm, multicenter, multicohort trial designed to evaluate the efficacy and safety of sevabertinib, an oral, reversible, small molecule TKI, in patients with pretreated, unresectable, or metastatic, nonsquamous NSCLC with HER2 (ERBB2) TKD–activating mutations.3 HER2 (ERBB2) activating mutations were determined in blood or tumor tissue by local laboratories before enrollment.
The primary efficacy end points were confirmed ORR and DOR according to blinded independent central review per RECIST 1.1 criteria.
What were the baseline characteristics of patients enrolled in cohort F?
The median age of patients in the study was 65 years old (range, 31-82) and most patients were female (n = 46; 63%), from Asia (n = 49; 67%) and identified as Asian (n = 51; 70%).2 ECOG performance status was predominantly 1 (n = 54; 74%) and most patients were never smokers (n = 57; 78%). All but 2 patients had adenocarcinoma (n = 71; 97%) and HER2 TKD mutations (n = 71; 97%); 6 patients (8%) received prior systemic therapy. Prior therapy consisted of platinum-based chemotherapy alone (n = 3; 4%), platinum-based chemoimmunotherapy (n = 3; 4%), and anti–PD-(L)1 therapy alone (n = 3; 4%). Brain metastases were present in most patients (n = 64; 88%), and the most common activating mutation within HER2 was Y772_A775dupYVMA (n = 58; 79%).
What safety data were reported within cohort F?
The most common adverse effects (AEs) that were related to study treatment with sevabertinib included diarrhea (n = 61; 84%), rash (n = 37; 51%), paronychia (n = 16; 22%), stomatitis (n = 19; 26%), and anemia (n = 16; 22%). AEs were largely low grade (grade 1, 19%; grade 2, 55%), although grade 3 (21%), 4 (1%), and 5 (1%) events also occurred.
What data supported the earlier accelerated approval of sevabertinib in pretreated HER2-mutant NSCLC?
In November 2025, sevabertinib received accelerated approval from the FDA for patients with pretreated, advanced HER2-mutant NSCLC based on data from cohort D of SOHO-01.2,3 In cohort D, which included patients who had been pretreated without HER2-directed therapy (n = 70), the ORR and median DOR were 71% (95% CI, 59%-82%) and 9.2 months (95% CI, 6.3-15.0).3 In cohort E, which included patients who had previous exposure to HER2-directed antibody-drug conjugates (n = 52), the ORR and DOR were 38% (95% CI, 25%-53%) and 7.0 months (95% CI, 5.6-NE).
What other areas is sevabertinib being studied in?
Sevabertinib is also under evaluation in the phase 3 SOHO-02 (NCT06452277) and phase 2 panSOHO (NCT06760819) trials in previously untreated patients with HER2-mutant NSCLC and patients with metastatic or unresectable solid tumors with HER2 activating mutations, excluding those with advanced NSCLC, respectively.1
References
- FDA grants sevabertinib priority review as a first-line treatment for patients with HER2-mutant non-small cell lung cancer. News release. Bayer. May 18, 2026. Accessed May 18, 2026. https://www.bayer.com/media/en-us/fda-grants-sevabertinib-priority-review-as-a-first-line-treatment-for-patients-with-her2-mutant-non-small-cell-lung-cancer/
- Le X, Kim TM, Loong HH, et al. Sevabertinib in advanced HER2-mutant non-small cell lung cancer. N Engl J Med. 2025;393(18):1819-1832. doi:10.1056/NEJMoa2511065
- FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. FDA. November 19, 2025. Accessed May 18, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer
