{"entity":{"id":"zenocutuzumab","kind":"drug","name":"Zenocutuzumab","aka":[],"tldr":"Zenocutuzumab is the first drug for cancers driven by NRG1 gene fusions, working by blocking HER3 from receiving its growth signal.","summary":"Zenocutuzumab is a HER2xHER3 bispecific antibody that docks on HER2 and physically blocks neuregulin 1 (NRG1) from binding HER3, the 'dock and block' mechanism that shuts off the growth signal in tumours driven by NRG1 gene fusions. It received accelerated approval in December 2024 for NRG1-fusion NSCLC and pancreatic cancer on the eNRGy trial, and in Q2 2026 the label was expanded to NRG1-fusion cholangiocarcinoma. It is given intravenously at 750 mg every 2 weeks; diarrhoea, musculoskeletal pain, fatigue and infusion reactions are the main adverse events. NRG1 fusions are rare and easily missed by DNA-only panels, so RNA-based sequencing is needed to find eligible patients, and confirmatory data are still required. Merus developed it and Partner Therapeutics commercialises it. For a newcomer: the first drug for a rare fusion that can appear in several different cancers.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Zenocutuzumab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Zenocutuzumab"},{"label":"Bizengri label (openFDA): pancreatic indication and eNRGy study section","url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22BIZENGRI%22"},{"label":"FDA notice: accelerated approval of zenocutuzumab (4 December 2024)","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"label":"Schram et al., efficacy of zenocutuzumab in NRG1 fusion-positive cancer (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2405008"}],"tags":[],"related":["nrg1-fusion"],"cancers":["nsclc","pancreatic","kras-wild-type-pdac","cholangiocarcinoma","metastatic-pdac"],"sections":[],"technologies":["bispecific-antibody"],"targets":["her2","her3"],"drugs":[],"companies":["merus"],"institutions":[],"pathways":[],"terms":[],"trials":["nct02912949"],"people":[],"bottlenecks":[],"keyPapers":["paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025","paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018","paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019"],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer, regulators: the Bizengri label (effective 19 May 2026) indicates zenocutuzumab 750 mg every two weeks for advanced unresectable or metastatic pancreatic adenocarcinoma with an NRG1 gene fusion after prior systemic therapy, under accelerated approval granted on 4 December 2024 on the eNRGy study (30 pancreatic patients in the label cohort; 15 of 36 responses, 42 percent, in the NEJM 2025 report). The EMA product page did not exist on 24 September 2026 (the corpus records a marketing authorisation application under evaluation) and NICE had no appraisal, so the drug is available in Europe only through trials or named-patient routes. NRG1 fusions are found almost only in KRAS wild-type tumours and need RNA-based sequencing.","Pancreatic ductal adenocarcinoma biomarkers: eligibility is an NRG1 fusion, found in 0.3 to 1% of pancreatic cancers and 1.3% of KRAS wild-type tumours, and detected reliably only by RNA-based or intron-covering sequencing; eNRGy gave responses in 15 of 36 pancreatic patients, 42% (Schram 2025)."],"brand":"Bizengri","modality":"Bispecific antibody (HER2×HER3)","mechanism":"Docks on HER2 and blocks NRG1 binding to HER3 ('dock and block').","approvals":[{"region":"US","year":2024,"indication":"NRG1-fusion NSCLC and pancreatic adenocarcinoma"},{"region":"US","year":2026,"indication":"NRG1-fusion cholangiocarcinoma"}],"mechanismSteps":["One arm docks on HER2","The other arm blocks the NRG1-binding site on HER3","NRG1 fusion protein cannot activate HER2/HER3 heterodimers","PI3K/AKT signalling collapses in NRG1-fusion tumours","Tumour regresses"],"dosing":{"route":"IV infusion","schedule":"750 mg every 2 weeks","modifications":"Hold for infusion reactions and LVEF decline","monitoring":"LVEF; infusion reactions; embryo-fetal toxicity","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Diarrhoea"},{"event":"Musculoskeletal pain"},{"event":"Fatigue"},{"event":"Nausea"},{"event":"Infusion-related reactions"},{"event":"Dyspnoea"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-12-04","type":"accelerated-approval","region":"US","note":"Accelerated approval, NRG1-fusion NSCLC and pancreatic adenocarcinoma (eNRGy): first therapy for NRG1 fusions The confirmatory requirement was still open 1.8 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy."},{"date":"2024-12-04","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 1.8 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic","indication":"Treatment of adults with advanced unresectable or metastatic nonsmall cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy."},{"date":"2026-Q2","type":"approval","region":"US","note":"NRG1-fusion cholangiocarcinoma","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/zenocutuzumab/","neighbours":{"biomarker":[{"id":"nrg1-fusion","kind":"biomarker","name":"NRG1 gene fusion","route":"/biomarkers/nrg1-fusion/"}],"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"invasive-mucinous-adenocarcinoma-lung","kind":"cancer","name":"Invasive mucinous adenocarcinoma of the lung","route":"/cancers/invasive-mucinous-adenocarcinoma-lung/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"her3","kind":"target","name":"HER3","route":"/targets/her3/"},{"id":"nrg1","kind":"target","name":"NRG1","route":"/targets/nrg1/"}],"company":[{"id":"merus","kind":"company","name":"Merus","route":"/companies/merus/"}],"trial":[{"id":"nct02912949","kind":"trial","name":"A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)","route":"/trials/nct02912949/"}],"paper":[{"id":"paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025","kind":"paper","name":"eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer","route":"/key-papers/paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025/"},{"id":"paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018","kind":"paper","name":"Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer","route":"/key-papers/paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018/"},{"id":"paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019","kind":"paper","name":"Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma","route":"/key-papers/paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"term":[{"id":"pancreatic-cancer-uk-drug-access","kind":"term","name":"Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)","route":"/terms/pancreatic-cancer-uk-drug-access/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}]}}