Continued zenocutuzumab treatment beyond progression in patients with NRG1+ pancreatic cancer and cholangiocarcinoma: Analysis from the phase 2 eNRGy trial.

作者：Alison M. Schram, Olumide B. Gbolahan, C. Neuzillet, Dirk Arnold, Antoine Hollebecque, Richard Greil, Mohammed Najeeb Al Hallak, Jordi Rodon Ahnert, Kim Anna Reiss, P. La Porte, Tormod Kyrre Guren, Carolyn Elizabeth Ragsdale, F. H. Garner, Alejandro D. Ricart, Shola Adeyemi, Christoph Springfeld · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.2_suppl.703 · 被引用次数：1 · 研究领域：HER2/EGFR in Cancer Research、Monoclonal and Polyclonal Antibodies Research、Fibroblast Growth Factor Research

703 Background: While progressive disease (PD) is often considered a surrogate for treatment failure, continued therapy beyond progression may offer clinical benefit, particularly in cancers with limited effective treatment options. This approach may be justified in cases of mixed response, indolent progression, or isolated progression amenable to local intervention. Zenocutuzumab, a HER2×HER3 bispecific antibody that blocks HER3-mediated NRG1 signaling and HER2/HER3 dimerization, is the first and only targeted therapy for NRG1+ cancers (FDA approved for previously treated, advanced NRG1+ NSCLC and pancreatic adenocarcinoma [PDAC]). We report an analysis of patients with advanced NRG1+ PDAC and cholangiocarcinoma (CCA) who continued zenocutuzumab beyond progression. Methods: eNRGy is an ongoing, open-label, single-arm, phase 2 trial of zenocutuzumab in advanced NRG1+ cancers. Patients are ≥18 y, previously treated with or not a candidate for other therapy, ECOG PS ≤2, and have measurable or evaluable disease per RECIST v1.1. Zenocutuzumab (750 mg IV every 2 weeks) is administered until PD or unacceptable toxicity. Treatment can continue beyond PD when clinical benefit is considered possible based on investigator assessment. In this post hoc analysis, we report data from patients with gastrointestinal (GI) tumors who received ≥3 doses of zenocutuzumab post-PD. Results: As of June 2025, 17 patients with advanced NRG1+ GI tumors (PDAC n=12, CCA n=5) continued zenocutuzumab after...