Sponsor: Bayer (industry)
Phase: 2
Start date: Feb. 13, 2025
Planned enrollment: 111
BAY 2927088, now named sevabertinib and marketed in the United States as Hyrnuo, is an oral HER2-directed tyrosine kinase inhibitor developed by Bayer. It is no longer investigational for its approved U.S. indication: the FDA granted accelerated approval in November 2025 for previously treated HER2-mutant, locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC), and expanded the indication in September 2026 to include patients without prior systemic therapy. Continued approval may depend on confirmation of clinical benefit. (fda.gov)
Sevabertinib is a reversible inhibitor of HER2 (ERBB2) that also inhibits mutant EGFR while showing relative selectivity over wild-type EGFR. It suppresses HER2 phosphorylation and downstream signaling. Preclinical activity has been demonstrated against HER2 exon 20 insertions, other activating HER2 mutations, and HER2-amplified models. (pmc.ncbi.nlm.nih.gov)
Evidence comes principally from SOHO-01, an open-label, single-arm phase I/II trial:
These results are from non-randomized cohorts; randomized confirmatory evidence remains important for establishing effects on progression-free and overall survival.
Among 136 previously treated patients, the most frequent adverse reactions were diarrhea (87%; grade 3/4, 18%), rash (66%), paronychia (33%), stomatitis (29%), and nausea (21%). Serious adverse reactions occurred in 31%; dose reductions occurred in 28%, and 3.7% discontinued treatment because of adverse reactions. (accessdata.fda.gov)
Important labeled risks include diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, cardiac dysfunction, ocular toxicity, pancreatic-enzyme elevations, and embryo-fetal toxicity. (accessdata.fda.gov)
Last updated: Sep 2026
Goal: Evaluate the antitumor activity and safety of sevabertinib in HER2-mutant solid tumors other than non-small cell lung cancer (NSCLC).
Patients: Adults with measurable, locally advanced unresectable or metastatic solid tumors harboring an activating HER2 mutation who have received appropriate standard therapy or lack satisfactory alternatives. Eligible tumor types include colorectal, biliary tract, bladder or urothelial, cervical, endometrial, and other solid cancers; NSCLC is excluded. Prior HER2 tyrosine kinase inhibitor treatment and active brain metastases are exclusion criteria.
Design: Open-label, nonrandomized, single-arm basket study enrolling patients across tumor types. Treatment continues until RECIST 1.1 progression, unacceptable toxicity, or withdrawal.
Treatments: All participants receive oral sevabertinib (BAY 2927088) 20 mg twice daily in repeated 3-week cycles. Sevabertinib is a reversible HER2-directed tyrosine kinase inhibitor that suppresses signaling from activating HER2 mutations. In separate, nonrandomized NSCLC cohorts, confirmed objective response rates ranged from 38% to 75% depending on prior treatment; these results do not establish its efficacy in the non-NSCLC tumors studied here.
Outcomes: The primary endpoint is confirmed objective response rate by RECIST 1.1 on blinded independent central review. Secondary endpoints include response duration and time to response, disease control, progression-free and overall survival, investigator-assessed response measures, adverse events and treatment discontinuations, and patient-reported physical functioning and quality of life.
Burden on patient: Estimated moderate burden. Twice-daily treatment is taken at home, but repeated clinic visits for imaging, cardiac assessments (echocardiography or cardiac MRI and ECG), blood and urine testing, physical examinations, and quality-of-life questionnaires add time and travel. No mandatory research biopsies or intensive pharmacokinetic sampling are described.
Last updated: Sep 2026
Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.
Inclusion Criteria:
* Documented histologically or cytologically confirmed locally advanced, unresectable or metastatic solid tumor cancer (colorectal carcinoma; biliary tract cancer; bladder and urothelial tract cancer; cervical cancer; endometrial cancer; other solid tumor cancer, excluding NSCLC)
* Participant must be ≥18 years of age or over the legal age of consent
* Patients who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments
* Documented activating HER2 mutation
* At least one measurable lesion that would qualify as a target lesion by RECIST 1.1 criteria
Exclusion Criteria:
* Primary diagnosis of non-small cell lung cancer (NSCLC)
* Prior treatment with a HER2 tyrosine kinase inhibitor (TKI)
* Active brain metastases
* Uncontrolled, severe, intercurrent illness
Sydney, New South Wales, 2109, Australia
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Blacktown, New South Wales, 2148, Australia
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Southport, Queensland, 4215, Australia
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Halifax, Nova Scotia, B3H 1V7, Canada
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Toronto, Ontario, M5G 2C4, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Shanghai, 200000, China
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Beijing, Beijing Municipality, 100142, China
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Beijing, Beijing Municipality, 100034, China
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Changsha, Hunan, 410013, China
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Shanghai, Shanghai Municipality, 200032, China
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Hangzhou, Zhejiang, 310016, China
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Copenhagen, Capital Region, 2100, Denmark
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Aarhus N, Central Jutland, 8200, Denmark
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Odense, Region Syddanmark, 5000, Denmark
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Pierre-Bénite, Auvergne-Rhône-Alpes, 69310, France
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Brest, Brittany Region, 29200, France
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Lille, Hauts-de-France, 59000, France
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Bordeaux, New Aquitaine, 33000, France
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Montpellier, Occitanie, 34298, France
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Villejuif, Île-de-France Region, 94805, France
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Reggio Emilia, 42123, Italy
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Milan, 20133, Italy
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Roma, 00168, Italy
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Milan, 20141, Italy
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Nagoya, Aichi-ken, 464-8681, Japan
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Kashiwa, Chiba, 277-8577, Japan
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Sapporo, Hokkaido, 060-8648, Japan
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Sakai, Osaka, 590-0197, Japan
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Chuo-ku, Tokyo, 104-0045, Japan
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Koto-ku, Tokyo, 135-8550, Japan
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Seoul, 06351, South Korea
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Seoul, Seoul Teugbyeolsi, 05505, South Korea
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Seoul, Seoul Teugbyeolsi, 3080, South Korea
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Seoul, Seoul Teugbyeolsi, 03722, South Korea
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Barcelona, 08035, Spain
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Madrid, 28040, Spain
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Barcelona, 08028, Spain
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L'Hospitalet de Llobregat, Barcelona, 08908, Spain
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Madrid, Navarre, 28027, Spain
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Geneva, 1205, Switzerland
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Bern, 3010, Switzerland
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Zurich, 8091, Switzerland
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Birmingham, Alabama, 35233, United States
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Duarte, California, 91010, United States
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Fort Myers, Florida, 33908, United States
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Boston, Massachusetts, 02215, United States
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Farmington Hills, Michigan, 48334, United States
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Cleveland, Ohio, 44195, United States
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Nashville, Tennessee, 37203, United States
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Houston, Texas, 77030, United States
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Madison, Wisconsin, 53792, United States
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Detroit, Michigan, 48202, United States
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Status: Withdrawn
Seattle, Washington, 98195, United States
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Status: Withdrawn