CRESTONE: A Phase II Study of the Efficacy and Safety of the HER3 Monoclonal Antibody, Seribantumab, in Solid Tumors With Neuregulin-1 (NRG1) Fusions
Recommended Citation
Patil T, Lin JJ, Cheema PK, Carrizosa DR, Burkard ME, Elamin YY, Desai J, Patel JD, Nagasaka M, Reckamp KL, Waqar SN, Bauman JR, Schram AM, Gadgeel SM, Ma PC, Konduri K, Nguyen D, Misleh J, Bleeker J, Weiss M, Thavaneswaran S, Haura EB, Deegan M, Kaufman J, Srivastava J, Jansen VM, and Liu SV. 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 Precis Oncol 2025;9:e2500221.
Document Type
Article
Publication Date
8-1-2025
Publication Title
JCO Precis Oncol
Keywords
Humans, Female, Middle Aged, Male, Neuregulin-1, Aged, Neoplasms, Adult, Antibodies, Monoclonal, Humanized, Prospective Studies, Receptor, ErbB-3, Antibodies, Monoclonal, Aged, 80 and over
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.
Medical Subject Headings
Humans; Female; Middle Aged; Male; Neuregulin-1; Aged; Neoplasms; Adult; Antibodies, Monoclonal, Humanized; Prospective Studies; Receptor, ErbB-3; Antibodies, Monoclonal; Aged, 80 and over
PubMed ID
41428976
Volume
9
First Page
2500221
Last Page
2500221
