| Title: |
Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer |
| Authors: |
Schram, Alison M.; Goto, Koichi; Kim, Dong-Wan; Macarulla, Teresa; Hollebecque, Antoine; O'Reilly, Eileen M.; Ou, Sai-Hong Ignatius; Rodon, Jordi; Rha, Sun Young; Nishino, Kazumi; Duruisseaux, Michael; Park, Joon Oh; Neuzillet, Cindy; Liu, Stephen V.; Weinberg, Benjamin A.; Cleary, James M.; Calvo, Emiliano; Umemoto, Kumiko; Nagasaka, Misako; Springfeld, Christoph; Bekaii-Saab, Tanios; O'Kane, Grainne M.; Opdam, Frans; Reiss, Kim A.; Joe, Andrew K.; Wasserman, Ernesto; Stalbovskaya, Viktoriya; Ford, Jim; Adeyemi, Shola; Jain, Lokesh; Jauhari, Shekeab; Drilon, Alexander |
| Contributors: |
Kim, Dong-Wan |
| Publisher Information: |
Massachusetts Medical Society |
| Publication Year: |
2025 |
| Collection: |
Seoul National University: S-Space |
| Subject Terms: |
GAMMA-HEREGULIN; TUMORS; GENE |
| Description: |
BACKGROUND Neuregulin 1 (NRG1) fusions are recurrent oncogenic drivers found in multiple solid tumors. NRG1 binds to human epidermal growth factor receptor 3 (HER3), leading to heterodimerization with HER2 and activation of downstream growth and proliferation pathways. The efficacy and safety of zenocutuzumab, a bispecific antibody against HER2 and HER3, in patients with NRG1 fusion-positive solid tumors are unclear. METHODS In this registrational, phase 2 clinical study, we assigned patients with advanced NRG1 fusion-positive cancer involving any tumor type to receive zenocutuzumab at a dose of 750 mg intravenously every 2 weeks. The primary end point was overall response (complete or partial response) according to investigator assessment. Secondary end points included duration of response, progression-free survival, and safety. RESULTS A total of 204 patients with 12 tumor types were enrolled and treated. Among 158 patients who had measurable disease and were enrolled at least 24 weeks before the data-cutoff date, a response occurred in 30% (95% confidence interval [CI], 23 to 37). The median duration of response was 11.1 months (95% CI, 7.4 to 12.9); 19% of responses were ongoing at the data-cutoff date. Responses were observed in multiple tumor types - including in 27 of 93 patients (29%; 95% CI, 20 to 39) with non-small-cell lung cancer (NSCLC) and 15 of 36 patients (42%; 95% CI, 25 to 59) with pancreatic cancer - and across multiple NRG1 fusion partners. The median progression-free survival was 6.8 months (95% CI, 5.5 to 9.1). Adverse events were primarily grade 1 or 2. The most common adverse events that were considered by the investigator to be related to zenocutuzumab were diarrhea (in 18% of the patients), fatigue (in 12%), and nausea (in 11%). Infusion-related reactions (composite term) were observed in 14% of the patients. One patient discontinued zenocutuzumab owing to a treatment-related adverse event. CONCLUSIONS Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion-positive cancer, ... |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| ISBN: |
978-0-01-415991-8; 0-01-415991-0 |
| Relation: |
https://hdl.handle.net/10371/217409; 001415991000002; 234454 |
| DOI: |
10.1056/NEJMoa2405008 |
| Availability: |
https://hdl.handle.net/10371/217409; https://doi.org/10.1056/NEJMoa2405008 |
| Accession Number: |
edsbas.117FFB2A |
| Database: |
BASE |