Findings from a post hoc analysis of an eNRGy trial evaluating treatment beyond progression with zenocutuzumab in patients with advanced neuregulin 1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC), suggest positive outcomes.
Results were presented at the 2026 International Association for the Study of Lung Cancer (IASLC) Targeted Therapies of Lung Cancer (TTLC) meeting.
NRG1+ NSCLC is associated with low response rates and poor outcomes with non-targeted therapies, underscoring the need for effective targeted treatment options such as zenocutuzumab and potential use beyond progression.
‘Patients with advanced NRG1 fusion-positive non-small cell lung cancer often have limited treatment options after progression,’ said Dr Misako Nagasaka, MD, PhD of the University of California Irvine and senior author.
‘In this analysis, continued zenocutuzumab treatment beyond RECIST progression provided meaningful, sometimes long-lasting, clinical benefit while maintaining a favourable tolerability profile.’
The analysis included 27 patients with NRG1+ NSCLC who received at least three doses of zenocutuzumab after radiographic progression.
Oligoprogression occurred in 81% of patients, while 19% experienced diffuse progression. Median total zenocutuzumab exposure increased to nearly 10 months, compared with approximately seven months before progression.
Eight patients continued treatment for more than six months beyond progression, including one patient remaining on zenocutuzumab for more than 23 months after progression, with treatment still ongoing as of December 2025.
Another patient remained on zenocutuzumab for nearly four years in total. Additionally, 22% of patients were able to continue zenocutuzumab following local management of progressing lesions including radiotherapy, gamma knife surgery, and surgical resection. Treatment was generally well tolerated, and no patients discontinued therapy due to adverse events.
In December 2024, zenocutuzumab-zbco (Bizengri®) received US Food and Drug Administration accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harbouring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The indications were approved under accelerated approval based on ORR and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). NRG1 gene fusions and other gene fusions are best detected using the combination of tissue-based DNA and RNA next-generation sequencing.
About NRG1 Gene Fusions
NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerisation and activate downstream signalling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerisation and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably the combination of tissue-based DNA and RNA next generation sequencing, is essential to identify rare and actionable gene fusions like NRG1.
