CRESTONE: A Phase II Study of the Efficacy and Safety of the HER3 Monoclonal Antibody, Seribantumab, in Solid Tumors With Neuregulin-1 (NRG1) Fusions
- Author(s)
- 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; Liu, SV;
- Journal Title
- JCO Precision Oncology
- Publication Type
- Research article
- 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.
- Publisher
- American Society of Clinical Oncology
- Keywords
- Humans; Female; Middle Aged; Male; *Neuregulin-1/genetics; Aged; *Neoplasms/drug therapy/genetics; Adult; *Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects; Prospective Studies; *Receptor, ErbB-3/antagonists & inhibitors; *Antibodies, Monoclonal/therapeutic use/adverse effects; Aged, 80 and over
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1200/po-25-00221
- Open Access at Publisher's Site
https://doi.org/10.1200/po-25-00221- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-13 05:40:51
Last Modified: 2026-01-13 05:41:14