New Pill for a Gene-Related Advanced Lung Cancer

Hyrnuo (sevabertinib; pronounced Her noo' oh) is an oral, reversible HER2 tyrosine-kinase inhibitor. It is not a HER2 antibody and it is not for “HER2-positive” lung cancer in the breast-cancer IHC sense. The labelled molecular class in the United States and Canada is a HER2 (ERBB2) tyrosine kinase domain activating mutation — most often an exon 20 insertion such as YVMA.

The FDA granted accelerated approval on 19 November 2025. Health Canada issued a Notice of Compliance with Conditions on 29 January 2026; Bayer notified first sale on 24 April 2026. The UK MHRA granted a marketing authorisation to Bayer PLC on 1 April 2026. Japan’s MHLW approved ヒアニュオ on 24 August 2026 for HER2 mutation-positive unresectable advanced or recurrent NSCLC, without a prior-therapy restriction in the PMDA table. China’s NMPA approval is a company announcement until nmpa.gov.cn is retrieved.

US and Canadian labels are after prior systemic therapy. Do not treat Japan’s first-line wording as the North American prescription.

This is not a cure. Continued US approval depends on a confirmatory trial. Canada’s NOC/c is the same idea: promising evidence, more data required.

Where this is taking place

SOHO-01 (NCT05099172) — Phase 1/2, open-label, multi-cohort, still listed RECRUITING (CT.gov verified 10 Aug 2026). Sponsor: Bayer. Estimated enrolment 400. No Canadian sites on CT.gov. Countries with sites include China, the United States, Japan, Italy, France, South Korea, Spain, Taiwan, Brazil, Hong Kong, the Netherlands, Singapore, Belgium, Israel, Poland, and Portugal. Expansion groups include previously treated HER2-mutant NSCLC naïve to HER2-targeted therapy (Group D), prior HER2 ADC (Group E), and treatment-naïve disease (Group F). Group F is not the US or Canadian labelled indication.

SOHO-02 (NCT06452277 / Study 22615) — Phase 3 confirmatory first-line trial. RECRUITING (verified 24 Jul 2026). Sevabertinib 20 mg twice daily vs pembrolizumab plus platinum/pemetrexed. Estimated n=444. Non-squamous NSCLC with a HER2 TKD activating mutation; no prior systemic therapy for advanced disease. 270 locations / 36 countries. Canadian sites on CT.gov: BC Cancer (Vancouver) COMPLETED; Brampton Civic Hospital (Brampton, Ontario) RECRUITING; Princess Margaret Cancer Centre (Toronto) RECRUITING; Jewish General Hospital (Montreal) RECRUITING. This is a first-line randomisation, not a commercial script for someone already treated.

panSOHO (NCT06760819) — Phase 2 basket in other solid tumours with HER2-activating mutations. NSCLC is an exclusion. Not an enrolment path for this article.

NCT06761976 — Bayer expanded-access program, status AVAILABLE, for previously treated locally advanced or metastatic HER2-mutant NSCLC with no other therapeutic option. CT.gov lists no sites. Not the Access Level of this piece. Not a Canadian door for a labelled, marketed DIN.

Commercial supply (labelled, post-prior-therapy unless noted): United States, Canada (marketed), United Kingdom (MHRA). Japan: in-country after MHLW, broader indication on the PMDA table. China: company NMPA. European Union: no EC licence found.

Approval matrix

Access by country

• United States: Thoracic oncologist. FDA-labelled 19 Nov 2025 for adults with locally advanced or metastatic non-squamous NSCLC, HER2 TKD activating mutation on an FDA-approved test, after prior systemic therapy. 20 mg (two 10 mg tablets) twice daily with food. Swallow whole. USPI does not mandate a REMS or specialty pharmacy; retail vs specialty is unknown from the label. Bayer US: HYRNUO-us.com or 1-888-842-2937 (USPI). No copay dollars here. Prior authorization still applies. First-line is not labelled.
• Canada (zoom, not a different Access Level): Authorized with conditions (NOC/c) and marketed (DIN 02563444; first sale 24 Apr 2026). Adult locally advanced or metastatic NSCLC, HER2 TKD activating mutation on a validated test, after prior systemic therapy. Ask the lung-cancer specialist for a prescription. Authorized ≠ funded. CDA-AMC and pCPA listing status unknown / not confirmed on this page. Provincial / territorial / NIHB / RAMQ listing unknown / not confirmed on this page. SAP is the wrong door for a labelled, marketed product. Bayer Canada Medical Information: 1-800-265-7382 or canada.medinfo@bayer.com (Product Monograph) — that is medical information, not a copay program. First-line patients are not on the Canadian label; SOHO-02 is the 1L trial door (three recruiting Canadian sites above). Do not mail-order a US bottle.
• United Kingdom: MHRA authorised 1 Apr 2026. The GOV.UK body is prior-treatment / HER2 mutations, not IHC “HER2-positive.” NICE GID-TA11814 is awaiting development, not a recommendation. Ask the NSCLC clinic; do not assume NHS routine funding. SMC not found.
• European Union: No EC marketing authorisation found. SOHO-02 is recruiting in multiple EU countries as a first-line trial. Documented expanded access (NCT06761976) exists on paper with no CT.gov sites. Named-patient import is a specialist/legal plan, not a DIY order. Do not treat CHMP as a licence; none was found.
• Japan: In-country commercial after MHLW 24 Aug 2026. PMDA table: HER2 mutation-positive unresectable advanced or recurrent NSCLC, no line restriction in the table. Company says 1L is included. NHI unknown. Not a Canadian or US travel path, and not the North American label.
• China: In-country commercial per Bayer (赫新诺). NMPA page not retrieved. After one prior systemic therapy on the company indication. NRDL not found. Not a Canadian travel path.
• Australia / Switzerland / Israel: Authorisation not found on documents checked. Specialist + local special-access / trial if those programs apply.

If your regulator has not authorised it: do not import on your own. Ask about travelling to a labelled market (US, Canada, UK, Japan) only as a plan with both specialists.

Who is eligible (from the labels — they are not the same)

This is a mutation conversation, not a HER2-protein (IHC) conversation. HER2 amplification or overexpression without a TKD activating mutation is not the US or Canadian indication.

United States (USPI):

• Adult.
• Locally advanced or metastatic non-squamous NSCLC.
• Tumour has a HER2 (ERBB2) TKD activating mutation, as detected by an FDA-approved test.
• Has received a prior systemic therapy.
• Take 20 mg twice daily with food until progression or unacceptable toxicity.

Canada (Product Monograph / SBD):

• Adult.
• Locally advanced or metastatic NSCLC (the authorised sentence does not say non-squamous).
• Tumours have HER2 (ERBB2) TKD activating mutations.
• Has received a prior systemic therapy.
• Confirm the mutation with a validated test before starting.
• Same dose: 20 mg (two 10 mg tablets) twice daily with food.
• NOC/c: patients should be told the authorisation is with conditions. An improvement in survival has not been established.
• Hypersensitivity to sevabertinib or any tablet ingredient is a contraindication on the Canadian PM (the USPI lists none).
• Pediatrics: not authorised. Geriatrics: HC says numbers were too small to know if older adults respond differently.

Japan (PMDA table, not the US label):

• HER2 (ERBB2) gene mutation-positive unresectable advanced or recurrent NSCLC.
• Table row does not require prior systemic therapy and does not restrict to TKD. Company says all lines including 1L, and not limited by mutation subtype. That sentence does not travel to a Canadian or US clinic.

United Kingdom (GOV.UK news pending SmPC):

• Adults with advanced NSCLC with HER2 mutations that has spread or cannot be removed, after prior treatment, with testing before start. Treat the headline “HER2-positive” as sloppy until the SmPC is in hand.

Not labelled in the US or Canada:

• First-line / untreated advanced disease (Japan table and SOHO-02 / SOHO-01 Group F are different conversations).
• Squamous NSCLC on the US line (Canada’s sentence does not say non-squamous; SBD noted squamous data were limited).
• HER2 mutations outside the TKD on the US/Canada lines.
• Children.
• Other solid tumours (panSOHO is a trial, not a label).

What the pivotal study showed (label vs journal)

Use the label of the country that will prescribe.

FDA / USPI (SOHO-01 Groups D and E, HER2 TKD, non-squamous):

• Group D, n=70, prior systemic therapy, naïve to HER2-targeted therapy: ORR 71% (95% CI 59–82); complete response 2.9%; partial response 69%; median DOR 9.2 months (95% CI 6.3–15.0); DOR ≥6 months in 54% of responders; DOR ≥12 months in 18%. Median age 59; 67% female; 70% Asian; all adenocarcinoma; 91% stage IV; 20% stable brain metastases; 70% YVMA exon 20 insertion; 94% prior platinum; 71% prior immunotherapy.
• Group E, n=52, prior HER2-targeted ADC: ORR 38% (95% CI 25–53); median DOR 7 months (95% CI 5.6–NE); DOR ≥6 months in 60% of responders.

Health Canada PM / SBD (14 Oct 2024 cut, TKD subgroup):

• Group D TKD n=73: ORR 65.8% (95% CI 53.7–76.5); median DOR 6.8 months (95% CI 5.2–NE); DOR ≥6 months in 27.1% of responders. Disease control rate 82.2%. These numbers are not the FDA table.

NEJM (Le et al., 17 Oct 2025; later data-cut in the paper): Cohort D n=81 ORR 64%; Cohort E n=55 ORR 38%; Cohort F (untreated) n=73 ORR 71%, median DOR 11.0 months. Cohort F is not the US or Canadian indication.

This is tumour shrinkage and response duration on a single-arm trial, not a proven survival win. The confirmatory trial is SOHO-02.

How it is taken (labelled)

20 mg (two 10 mg red-brown tablets marked SE / 10) by mouth twice daily, with food, until the cancer grows or side effects are not manageable. Swallow whole. Do not cut, crush, or chew.

Missed dose: take when remembered before the next scheduled dose; do not double. Vomited dose: skip; take the next one on time.

Dose reductions (US and Canada): first → 10 mg twice daily; second → 10 mg once daily; stop if 10 mg once daily is not tolerated.

Strong CYP3A inhibitors: avoid; if unavoidable, cut the current total daily dose in half (US Table 3 / Canadian Table 3). Avoid strong and moderate CYP3A inducers (US); Canadian PM: strong CYP3A4 inducers not recommended. Avoid grapefruit and St John’s wort.

US: no dose adjustment described for mild hepatic or mild/moderate renal impairment; moderate/severe hepatic and severe renal unknown. Canada: moderate or severe hepatic impairment not recommended.

Companion diagnostic / HER2 TKD testing

Ask for HER2 (ERBB2) mutation testing of the tyrosine kinase domain, usually on a broad NGS panel of the tumour (sometimes plasma). This is not the HER2 IHC/FISH test used in breast cancer.

United States: the label requires an FDA-approved test. FDA contemporaneously approved the Oncomine Dx Target Test (Life Technologies Corporation / Thermo Fisher) as the companion diagnostic for HER2 TKD activating mutations in non-squamous NSCLC for sevabertinib. See FDA Companion Diagnostics. In SOHO-01, local labs enrolled patients; a retrospective Oncomine subset was almost entirely positive when evaluable.

Canada: confirm the mutation with a validated test before starting (PM). No named companion diagnostic on the monograph.

If prior NGS did not report ERBB2 / HER2 exon 20 insertions or other TKD mutations, ask whether the panel covers them.

Safety (from the USPI; Canadian PM is aligned on the same topics)

USPI boxed-style warnings and precautions (Highlights):

• Diarrhea: can be severe, with dehydration and electrolyte loss. Pooled 20 mg BID population (n=268): diarrhea 86%, Grade 3 15%. Median time to first onset four days. At the first loose stool or extra bowel movements, start an antidiarrheal (e.g. loperamide), increase fluids and electrolytes, and call the clinic. Have anti-diarrhea medicine before the first dose.
• Hepatotoxicity: monitor ALT, AST, and total bilirubin at baseline, every 2 weeks for the first month, then monthly as indicated. Pooled: hepatotoxicity 24% (3% Grade 3); lab ALT increase 35%, AST 35%.
• ILD / pneumonitis: can be severe. Pooled: two patients (0.7%), including 0.4% Grade 3. New or worsening shortness of breath, cough, or fever → call immediately. Permanently discontinue if ILD/pneumonitis is confirmed (any grade, US and Canada).
• Ocular toxicity: 14% pooled, including one Grade 3 case of corneal epithelial microcysts with temporary unilateral blindness. New eye symptoms → ophthalmology.
• Pancreatic enzyme elevation: lab amylase increase 32% (3.2% Grade 3–4); lipase 40% (10% Grade 3–4). Monitor amylase and lipase.
• Embryo-fetal toxicity: can cause fetal harm. Effective contraception for females and for males with female partners of reproductive potential during treatment and for 1 week after the last dose. Verify pregnancy before starting. Do not breastfeed during treatment and for 1 week after.

Most common adverse reactions (>20%) in the labelled SOHO-01 Groups D+E population (n=136, USPI): diarrhea, rash, paronychia, stomatitis, nausea. Grade 3–4 lab: decreased potassium, increased lipase, decreased lymphocytes, decreased sodium, increased amylase, increased ALT/AST.

Serious adverse reactions 31%; permanent discontinuation 3.7%.

Canadian PM Group D (n=81): diarrhea 84.0% (Grade 3 23.5%), rash 71.6%, paronychia 30.9%. ILD/pneumonitis 0.4% (one Grade 3) in the pooled 20 mg BID set on the Canadian warnings section.

US contraindications: none. Canada: hypersensitivity to the drug or any ingredient (the tablet contains lactose monohydrate).

Research team (Who)

Names below appear on NCT, label, SBD, or the NEJM paper.

• Bayer — sponsor (SOHO-01, SOHO-02, panSOHO, NCT06761976). US NDA holder: Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ. Canada MAH: Bayer Inc., Mississauga. UK MAH: Bayer PLC. Japan MAH: バイエル薬品株式会社.
• Xiuning Le, MD, PhD — first author, NEJM SOHO-01; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center (as in the NEJM/ESMO byline). Not listed as “overall official” on CT.gov.
• Tae Min Kim; Herbert H. Loong — NEJM co-authors (byline).
• Bayer Clinical Trials Contact — 1-888-842-2937, clinical-trials-contact@bayer.com (SOHO-01 / SOHO-02 / expanded-access CT.gov records).
• Life Technologies Corporation (Thermo Fisher) — Oncomine Dx Target Test, FDA companion diagnostic (FDA bulletin 19 Nov 2025).
• Koichi Goto, PhD — quoted in Bayer’s 24 Aug 2026 Japan announcement as Chief of Thoracic Oncology, National Cancer Center Hospital East. That is a company-quoted clinician, not a CT.gov principal investigator.

No Canadian principal investigator is named on the SOHO-01 record (no Canadian sites). SOHO-02 Canadian sites are listed as facilities, not as named PIs, on CT.gov.

How to talk to a doctor

Bring the NCT numbers and the label of the country you are in.

1. “Has my tumour been tested for a HER2 (ERBB2) tyrosine kinase domain activating mutation, not just HER2 IHC?”
2. “I have had prior systemic therapy. In the US/Canada, is Hyrnuo (sevabertinib) 20 mg twice daily with food the labelled next step, or is a HER2 ADC or another TKI the funded option?”
3. “If I have not had systemic therapy for advanced disease: the US and Canadian labels are after prior therapy. Is SOHO-02 (NCT06452277) open for me?” (Canada recruiting sites: Brampton Civic, Princess Margaret, Jewish General. Vancouver BC Cancer is listed completed.)
4. Diarrhea starts fast — “Do I leave with loperamide and a sick-day plan?”
5. Liver, pancreas labs, and new cough/breathlessness (ILD). Eye symptoms → ophthalmology.
6. Pregnancy, contraception for 1 week after the last dose, no breastfeeding for 1 week after.
7. Strong CYP3A drugs, grapefruit, St John’s wort.
8. Canada: “This is NOC/c, marketed, DIN 02563444. SAP is the wrong door. What is actually funded in this province? I do not have a listing answer.”
9. UK: “MHRA yes; NICE GID-TA11814 is awaiting development, not a yes.”
10. EU / Australia / Switzerland: “No licence found. Is the trial or Bayer expanded access (NCT06761976) the door, or a planned visit to a labelled country?”

Canada zoom: authorized with conditions, not funded-by-default

Health Canada has already authorised Hyrnuo, with conditions, and it is on the market. That is not a compassionate-access story. The remaining Canadian questions are who pays (unknown / not confirmed on this page) and line of therapy (the label is after prior systemic therapy; first-line is a trial). Do not call the clinic asking for SAP. Do not assume a provincial cancer-drug program has listed it because a DIN exists.

Bottom line

Sevabertinib is a labelled oral TKI for adults with advanced NSCLC and a HER2 TKD activating mutation after prior systemic therapy in the United States and Canada. The UK MHRA has authorised it for adults with advanced NSCLC with HER2 mutations that has progressed after prior treatment (GOV.UK body; SmPC not in hand). Japan’s PMDA table (24 Aug 2026) is HER2 mutation-positive unresectable advanced or recurrent NSCLC without a prior-therapy restriction — that sentence does not travel to a Canadian or US script. China’s NMPA date stays company until nmpa.gov.cn. Europe has no EC licence found. NICE is awaiting development, not a yes. Canada’s NOC/c is authorised-with-conditions, marketed, and not a funding decision. SAP is the wrong door. SOHO-02 is the first-line trial, with three recruiting Canadian sites. Authorized is not funded.

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Primary sources

1. FDA accelerated-approval bulletin, 19 Nov 2025 — https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer
2. USPI PDF, NDA 219972 — https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/219972Orig1s000Lbl.pdf
3. DailyMed HYRNUO (setid d7a11334-6e7a-445b-9a16-bdcd9acbe61f) — https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d7a11334-6e7a-445b-9a16-bdcd9acbe61f
4. FDA Companion Diagnostics — https://www.fda.gov/CompanionDiagnostics
5. Health Canada SBD for Hyrnuo (control 297051; DIN 02563444; NOC/c 2026-01-29; first sale 2026-04-24) — https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1783447155617
6. Health Canada DPD / DHPP product page (Marketed) — https://dhpp.hpfb-dgpsa.ca/dhpp/resource/106622
7. Canadian Product Monograph (HRES) — https://pdf.hres.ca/dpd_pm/00083323.PDF
8. Canadian Product Monograph (Bayer host, Date of Authorization 2026-01-29) — https://www.bayer.com/sites/default/files/2026-02/hyrnuo-pm-en.pdf
9. NOC/c Qualifying Notice, Hyrnuo 297051 — https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/notice-compliance/conditions/qualifying-notice-hyrnuo-297051.html
10. Health Canada NOC/c list (Hyrnuo row) — https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/notice-compliance/conditions.html
11. MHRA GOV.UK news, published 2 Apr 2026 (MA 1 Apr 2026, Bayer PLC) — https://www.gov.uk/government/news/sevabertinib-approved-to-treat-adults-with-her2-positive-lung-cancer-that-has-spread-or-cannot-be-removed-by-surgery
12. PMDA 承認品目一覧（新医薬品：2026年8月） — https://www.pmda.go.jp/files/000281577.pdf
13. Bayer Japan/global announcement, 24 Aug 2026 (company 1L claim; not the PMDA table) — https://www.bayer.com/media/en-us/bayers-sevabertinib-approved-in-japan-for-patients-with-her2-mutant-non-small-cell-lung-cancer/
14. Bayer China announcement, 15 Apr 2026 (company NMPA; 赫新诺) — https://www.bayer.com.cn/zh-hans/baierhexinnuoguoneihuopi
15. CPI reprint of NMPA conditional approval, 22 Apr 2026 (not nmpa.gov.cn) — https://www.cpi.ac.cn/zx/xyzl/202604/t20260422_429787.html
16. ClinicalTrials.gov SOHO-01 NCT05099172 — https://clinicaltrials.gov/study/NCT05099172
17. ClinicalTrials.gov SOHO-02 NCT06452277 — https://clinicaltrials.gov/study/NCT06452277
18. ClinicalTrials.gov expanded access NCT06761976 — https://clinicaltrials.gov/study/NCT06761976
19. ClinicalTrials.gov panSOHO NCT06760819 — https://clinicaltrials.gov/study/NCT06760819
20. Le X, Kim TM, Loong HH, et al. Sevabertinib in advanced HER2-mutant non–small-cell lung cancer. N Engl J Med. 2025;393:1819-1832. DOI 10.1056/NEJMoa2511065 (journal; not the label)
21. NICE GID-TA11814 / ID6616 (awaiting development; not a recommendation) — https://www.nice.org.uk/guidance/awaiting-development/gid-ta11814
22. Bayer US first-line sNDA Priority Review announcement, 18 May 2026 (application, not approval) — https://www.bayer.com/en/us/news-stories/new-drug-application-for-hyrnuo
23. Bayer Canada authorisation news, 2 Feb 2026 — https://www.bayer.com/en/ca/health-canada-grants-authorization-for-bayers-hyrnuo

Who (from sources)