Top KOLs Discussing SOHO-01
SOHO-01 Key Slides & Visuals
KOL Discussion Thread — Which HER2 Option First?
Sevabirtinib is now @FDA ✅ in 1L HER2/ERBB2 TKD mutated mNSCLC based off SOHO-01: - ORR: 75% - 73% of responding pts had DOR ≥ 6 months and 38% had ≥ 12 months - AEs: Diarrhea, LFTs, and Pneumonitis #Lcsm #WCLC26 #OncTwitter @OncUpdates
Zongertinib is super well tolerated, hope this will be the same and the price will come down some ( cough, cough)
Sevabertinib should be taken with meal. However under 12.3 Pharmacokinetics (effect on Food) high fat meal should be avoided. Not sure why it must be taken with meal since the solubility is almost zero above PH 4.5. Interesting
Now we have 3 options with zongertinib, TDXd and sevabirtinib, which one to choose first?
Zong better tolerated than Enhertu . No experience with Seva .
But enhertu has phase III daya behind it
SOHO-01 Top Tweets
𝕏Original Article: Sevabertinib in Advanced HER2-Mutant Non–Small-Cell Lung Cancer (SOHO-01 phase 1–2 study) https://t.co/j9U1z5qZAS #ESMO25 | @myESMO https://t.co/2ARAQUTjOd
𝕏PL04.03 - Safety and Efficacy of BAY 2927088 In HER2-Mutant NSCLC: Expansion Cohort from the Phase I/II SOHO-01 Study ORR=72.1% (90.0% among HER2 Y772_A775dup insertion) DOR=8.7 months Most common AE: Dirrhea (no report of ILD/pneumonitis) Impressive results! #WCLC24 https://t.co/DBwmNDBrdC
𝕏Our Dr. @LeXiuning presents a key update for patients with HER2 positive NSCLC from the phase 1/2 SOHO-01 study. BAY 2927088 -Oral reversible TKI -ORR 72% (90% in YMVA) -mDOR 8.7 mos -mPFS 7.5 mos -AE: 25% grade 3+ diarrhea #WCLC24 #LCSM @OncoAlert https://t.co/o2gyDIuuzo
𝕏SOHO-01 update on HER2 TKI sevabertinib in NSCLC presented by @LeXiuning ORR: - Pretreated 64% - Previous ADC 38% - Treatment naive 71% - Activity in 🧠 - Grade 3 diarrhea 28%; No ILD/pneumonitis. 👉 Phase III trial SOHO-02 in first-line now recruiting #ESMO25 #LCSM https://t.co/m3eh2t8N67
𝕏#lcsm friends Looks like between zongertinib and sevabertinib we got delivered twins at #ESMO25! Both look super cute, are very effective… at drawing attention and seem mild-mannered. One just poops a little more than the other😉 https://t.co/UIUsuy7WQI
𝕏#ESMO25 Update on SOHO-01 with sevabertinib (BAY 2927088) in #HER2 mutant NSCLC from Dr. @LeXiuning. In previously treated, HER2 mutant NSCLC, sevabertinib had RR 64%, DCR 81%, DOR 9.2m, PFS 8.3m. #ESMOAmbassadors https://t.co/XA24aiqCWb
𝕏Another brick in the wall of HER2 mut NSCLC. Promising efficacy of BAY in HER2 naive pts (ORR 70.5%) but also in pts treated with TDxD (ORR 35.3%). Diarrhea as the most frequent AE (almost all pts but no tt discontinuation). #ELCC25 @OncoAlert @nicogirardcurie https://t.co/Fc0KOS4Wvy
𝕏Sevabirtinib is now @FDA ✅ in 1L HER2/ERBB2 TKD mutated mNSCLC based off SOHO-01: - ORR: 75% - 73% of responding pts had DOR ≥ 6 months and 38% had ≥ 12 months - AEs: Diarrhea, LFTs, and Pneumonitis #Lcsm #WCLC26 #OncTwitter @OncUpdates https://t.co/Uj9jlKnE20
𝕏🆙 #WCLC26 #LCSM Mini Oral Session 🔥 SOHO-01: Molecular Landscape of Acquired Resistance to Sevabertinib in HER2-mutant NSCLC 🎯85 pts with paired BL-PD plasma NGS 🎯Resistance-associated events in 30.1% 🎯Secondary HER2 T862A 16.4%, HER2 amplification 2.7%; C805S not detected 🎯Bypass/downstream alterations less frequent (PIK3CA/PTEN, MAPK pathway, 12.3%) 🎙️ @LeXiuning 🔢 MO12.04 ☑️ NCT05099172 🔗 https://t.co/8SXWyqrxiE @OncoAlert @Larvol @IASLC
𝕏🔥#WCLC24 Presidential 2✴️ 🎙️@LeXiuning 🎯Safety and Efficacy of BAY 2927088 In Patients with HER2-Mutant NSCLC: Expansion Cohort from the Phase I/II SOHO-01 Study #LCSM @IASLC @OncoAlert https://t.co/Q5L0yj5oBa https://t.co/fMenyzAIia
FDA Approval — September 9, 2026
Trial Methodology & Results
Study Design
Phase 1/2, open-label, single-arm, multicenter, multi-cohort; dose escalation (10 mg QD to 40 mg BID) established 20 mg BID as the recommended dose for expansion.
Population
Advanced NSCLC with HER2 (ERBB2) activating mutations, identified in tumor tissue or plasma. Approval populations: HER2 TKD-mutant non-squamous NSCLC (1L: treatment-naive cohort N=69; 2L+: cohorts D/E).
Intervention
Sevabertinib 20 mg orally twice daily — an oral, reversible, potent and selective HER2 TKI — until progression or unacceptable toxicity.
Endpoints
Primary: confirmed ORR per RECIST v1.1 by BICR. Secondary: DoR, DCR, PFS (BICR and investigator), safety and tolerability.
Biomarker
HER2 (ERBB2) TKD activating mutations by FDA-authorized test; local tissue or plasma identification at enrollment.
Sponsor
Bayer. Confirmatory Phase 3: SOHO-02 (sevabertinib vs standard therapy, untreated HER2-mutant advanced NSCLC).
Efficacy
First-line (treatment-naive cohort, N=69, Sept 2026 approval): ORR 75% (CR 6%, PR 70%); DoR ≥6 months in 73% of responders and ≥12 months in 38%. Previously treated (Nov 2025 approval): cohort D ORR 71% with median DoR 9.2 months; cohort E (post-HER2-ADC) ORR 38%. Each value is labeled to its approval dataset — the cohorts are distinct populations within one ongoing trial.
ORR 75% first-line — accelerated approval in both 1L and 2L+ settingsSource: Bayer PR (1L) · OncLive (2L)
Safety
Per the Nov 2025 label discussion, the most common treatment-related adverse events were diarrhea, rash and paronychia. Physicians reacting to the 1L approval highlighted monitoring for diarrhea, hepatotoxicity and LV dysfunction (Dr. Martin Dietrich, verbatim in the sentiment table). Bayer reports the 1L safety profile was consistent with previous findings.
Source: OncLive (label AEs, Nov 2025) · Bayer PRResistance — WCLC 2026 exploratory analysis
MO12.04 (Le et al., WCLC 2026): among 73 evaluable patients with paired plasma NGS, putative resistance-associated genomic events emerged in 30.1%; secondary HER2 T862A was the predominant mechanism (16.4%), with bypass PIK3CA/PTEN and MAPK-pathway alterations in 12.3%. Most progressing patients lacked an identifiable genomic driver — and T862A carriers had comparable duration of response. Full abstract in the slide OCR above.
Source: WCLC 2026 (MO12.04) — via KOL Pulse conference coverageClinical Implications
✅ HER2 TKD-mutant NSCLC now has an FDA-approved oral TKI in both the first-line and previously treated settings — a subset (2–4% of NSCLC, often younger, predominantly female, never-smokers) that until 2025 had only ADC options. The approvals sharpen the case for comprehensive molecular testing (including HER2) at diagnosis, as lead investigator Xiuning Le emphasized in Bayer’s release. Accelerated-approval caveats apply: confirmation rests on Phase 3 SOHO-02.
Source: Bayer press release, Sept 9, 2026SOHO-01 in the News
SOHO-01 FAQ
What is the SOHO-01 trial?
SOHO-01 (NCT05099172) is an ongoing Phase 1/2, open-label, single-arm, multicenter, multi-cohort trial of sevabertinib (Hyrnuo, Bayer), an oral, reversible HER2 tyrosine kinase inhibitor, in advanced NSCLC with HER2 or EGFR mutations. After dose escalation established 20 mg twice daily, expansion cohorts enrolled HER2-mutant patients: cohort D (previously treated, HER2-therapy naive), cohort E (prior HER2-targeted ADCs), and cohort F (treatment-naive). Primary endpoint: objective response rate per RECIST v1.1 by blinded independent central review.
What did the FDA approve on September 9, 2026?
The FDA granted accelerated approval to sevabertinib for adults with locally advanced or metastatic non-squamous NSCLC whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test - expanding the November 2025 approval in previously treated patients to include first-line, treatment-naive patients. The 1L approval is based on SOHO-01's treatment-naive cohort (N=69): ORR 75% (complete responses in 6%, partial in 70%), with 73% of responders maintaining response at least 6 months and 38% at least 12 months.
What supported the earlier November 2025 approval?
The November 19, 2025 accelerated approval covered previously treated HER2-mutant NSCLC, based on SOHO-01 cohorts D and E: ORR 71% with median duration of response 9.2 months in HER2-therapy-naive previously treated patients, and ORR 38% in patients who had received prior HER2-targeted ADCs. Sevabertinib is also approved in China (NMPA) for previously treated HER2-mutant NSCLC.
Is the approval conditional?
Yes - both indications are accelerated approvals based on response rate and duration of response. Continued approval may be contingent on confirmatory evidence from the ongoing Phase 3 SOHO-02 trial, which compares sevabertinib against standard therapy in untreated advanced HER2-mutant NSCLC. Common adverse events reported with sevabertinib include diarrhea, rash and paronychia; physicians on this page also flagged hepatotoxicity and LV dysfunction monitoring.
How does resistance to sevabertinib develop?
Per the exploratory biomarker analysis presented at WCLC 2026 (MO12.04, Le et al.), paired plasma NGS in 73 evaluable patients found putative resistance-associated genomic events in 30.1%, with secondary HER2 T862A substitutions the most common (16.4%), followed by HER2 amplification; bypass alterations (PIK3CA/PTEN, MAPK pathway) occurred in 12.3%. Most progressing patients lacked an identifiable genomic driver, suggesting non-genetic mechanisms - and patients with T862A had comparable duration of response to those without.