Journal article
CRESTONE: A Phase II Study of the Efficacy and Safety of the HER3 Monoclonal Antibody, Seribantumab, in Solid Tumors With Neuregulin-1 ( NRG1 ) Fusions
JCO precision oncology, Vol.9, e2500221
08/2025
DOI: 10.1200/PO-25-00221
PMCID: PMC12736398
PMID: 41428976
Abstract
Purpose
Neuregulin-1 (NRG1) fusions are rare but actionable oncogenic drivers in solid tumors. Seribantumab is a fully human anti-HER3 IgG2 monoclonal antibody. In this report, we present the antitumor activity and safety data of seribantumab from the CRESTONE study (ClinicalTrials.gov identifier: NCT04383210).
Patients and Methods
This was a prospective phase II clinical study in which patients with advanced solid tumors harboring an NRG1 fusion received seribantumab at a dose of 3,000 mg intravenously once weekly. The primary end point was objective response rate (ORR) by RECIST v1.1. Secondary end points included safety, duration of response, progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). The study was terminated before full enrollment because of sponsor decision, unrelated to safety or efficacy.
Results
A total of 54 patients with nine different tumor types featuring 19 different NRG1 fusion partners were enrolled. For the 29 patients included in the primary efficacy analysis, the investigator-assessed ORR was 34.5% (95% CI, 17.9 to 54.3), with a DCR of 79% (95% CI, 60 to 92). The median PFS was 5.4 (95% CI, 3.9 to 10.8) months; the median OS was 20.3 (95% CI, 10.2 to not reached) months. In patients with non–small cell lung cancer, eight of 22 achieved response (ORR, 36.4%). Adverse events (AEs) were mostly grade 1 or 2. The most common treatment-related AEs were diarrhea (39%), fatigue (32%), and nausea (22%).
Conclusion
These results support the antitumor activity and safety of seribantumab in patients with advanced solid tumors harboring NRG1 fusions.
Details
- Title: Subtitle
- CRESTONE: A Phase II Study of the Efficacy and Safety of the HER3 Monoclonal Antibody, Seribantumab, in Solid Tumors With Neuregulin-1 ( NRG1 ) Fusions
- Creators
- Tejas Patil - University of Colorado Cancer CenterJessica J Lin - Massachusetts General HospitalParneet K Cheema - William Osler Health SystemDaniel R Carrizosa - Levine Cancer InstituteMark E Burkard - University of IowaYasir Y Elamin - The University of Texas MD Anderson Cancer CenterJayesh Desai - Peter MacCallum Cancer CentreJyoti D Patel - Northwestern UniversityMisako Nagasaka - University of California, IrvineKaren L Reckamp - Cedars-Sinai Medical CenterSaiama N Waqar - Washington University in St. LouisJessica R Bauman - Fox Chase Cancer CenterAlison M Schram - Memorial Sloan Kettering Cancer CenterShirish M Gadgeel - Henry Ford Health SystemPatrick C Ma - Pennsylvania State UniversityKartik Konduri - Texas OncologyDanny Nguyen - City Of Hope National Medical CenterJamal Misleh - Medical Oncology Hematology ConsultantsJonathan Bleeker - Sanford USD Medical CenterMatthias Weiss - ThedaCareSubotheni Thavaneswaran - St Vincent's Hospital SydneyEric B Haura - Moffitt Cancer CenterMaegan Deegan - ValoreJonathan Kaufman - ValoreJaya Srivastava - ValoreValerie M Jansen - ValoreStephen V Liu - Georgetown University
- Resource Type
- Journal article
- Publication Details
- JCO precision oncology, Vol.9, e2500221
- DOI
- 10.1200/PO-25-00221
- PMID
- 41428976
- PMCID
- PMC12736398
- NLM abbreviation
- JCO Precis Oncol
- ISSN
- 2473-4284
- eISSN
- 2473-4284
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Grant note
- Elevation Oncology, Inc.
Supported by Elevation Oncology, Inc.
- Language
- English
- Date published
- 08/2025
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985096041202771
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