BAY2927088

Overview

BAY2927088 (generic name: sevabertinib) is an investigational, oral, reversible tyrosine kinase inhibitor (TKI) being developed primarily for tumors with activating HER2 (ERBB2) mutations, especially non-small cell lung cancer (NSCLC). As of May 28, 2025, the FDA accepted an NDA and granted Priority Review for previously treated adults with HER2‑mutant NSCLC; China’s CDE accepted the NDA on July 28, 2025. Regulatory filings were supported by Phase I/II data from the SOHO‑01 trial. A global Phase III first‑line study (SOHO‑02; NCT06452277) and a Phase II basket study in HER2‑mutant solid tumors (panSOHO) are ongoing. (bayer.com)

Mechanism of action

• Oral, reversible, non‑covalent TKI that potently inhibits mutant HER2 (including exon 20 insertions and point mutations) and shows selectivity vs wild‑type EGFR; it also targets certain mutant EGFR variants. Preclinical data demonstrate strong activity across HER2 exon 20 insertion variants (e.g., A775insYVMA) and selected point mutations, with in vivo efficacy in HER2‑mutant xenografts. (aacrjournals.org)

Efficacy

Clinical evidence is from the ongoing Phase I/II SOHO‑01 trial (NCT05099172), including an expansion cohort in previously treated, HER2‑mutant NSCLC (dose: 20 mg twice daily):

• ASCO 2024 late‑breaking abstract (data cutoff Feb 19, 2024; n=34 treated; 33 evaluable): ORR 70% (23/33; 95% CI 51.3–84.4); disease control rate 82%; median time to response 5.7 weeks; median PFS 8.1 months (95% CI 4.4, not evaluable); median duration of response (DoR) not reached at cutoff. (ascopubs.org)
• WCLC 2024 Presidential Symposium presentation (n=44; 43 evaluable): confirmed ORR 72.1% (1 CR, 2.3%); median DoR 8.7 months (95% CI 4.5, NE); median PFS 7.5 months (95% CI 4.4, 12.2). In tumors with HER2 YVMA insertions, ORR 90.0%, DoR 9.7 months, PFS 9.9 months. (bayer.com)
• Bayer’s May 2025 Priority Review press release cites investigator‑assessed ORR 70.5% in one expansion cohort (Cohort D) and 35.3% in another (Cohort E) as of Oct 14, 2024 (different cohort definitions within SOHO‑01). (bayer.com)

Note: No Phase III efficacy results have been reported as of October 7, 2025. (bayer.com)

Safety

Across SOHO‑01:

• Common treatment‑related adverse events (TRAEs): diarrhea (≈85–86%; grade 3 ≈25%), rash (≈43–47%), and paronychia (≈25%). Grade ≥3 TRAEs were reported in 40.9%; discontinuation due to TRAEs in 6.8% (WCLC 2024 dataset). (bayer.com)
• ASCO 2024 reported diarrhea (85%, mostly grade 1–2) and rash (47%, mostly grade 1–2); 3 patients discontinued due to drug‑related AEs. (ascopubs.org)
• In the Priority Review press communication, diarrhea was the most common TRAE leading to dose reduction; no interstitial lung disease (ILD) cases were noted in the cited dataset. (bayer.com)

Ongoing trials

• SOHO‑02 (NCT06452277): Phase III, first‑line HER2‑mutant advanced NSCLC, sevabertinib vs platinum/pemetrexed + pembrolizumab; primary endpoint PFS by blinded independent central review. Recruiting. (bayer.com)
• SOHO‑01 (NCT05099172): Phase I/II, first‑in‑human study in advanced NSCLC with HER2/EGFR mutations; basis for current efficacy/safety data and expedited regulatory designations. (clinicaltrials.bayer.com)
• panSOHO (NCT06760819): Phase II basket in metastatic/unresectable HER2‑mutant solid tumors (non‑NSCLC). First patient enrolled March 4, 2025. (bayer.com)

Further reading

• ASCO 2024 late‑breaking abstract (SOHO‑01 expansion cohort). (ascopubs.org)
• AACR 2023 preclinical abstract on HER2‑mutant models. (aacrjournals.org)
• SOHO‑01 trial listing (sponsor site summary). (clinicaltrials.bayer.com)
• FDA Priority Review announcement (May 28, 2025). (bayer.com)
• Phase III SOHO‑02 trial announcement and design. (bayer.com)
• China CDE NDA acceptance (July 28, 2025). (bayer.com)

Notes - BAY2927088 and sevabertinib refer to the same drug. Data above come from conference abstracts and company communications; peer‑reviewed full manuscripts had not yet been identified for the pivotal SOHO‑01 expansion data as of October 7, 2025. (ascopubs.org)

Last updated: Oct 2025