Bizengri (zenocutuzumab-zbco) / Partner Therap, Genmab - LARVOL DELTA

Comparative Efficacy and Safety of Biomarker-Guided Targeted Therapies Versus Conventional Treatment in Advanced Biliary Tract Cancer: A Systematic Review and Network Meta-Analysis (ACG 2026) - "14 studies involving 3,842 patients were included, comprising 2,116 males (55.1%) and 1,726 females (44.9%), with median age ranging from 58â69 years. Evaluated therapies included FGFR inhibitors (pemigatinib, futibatinib, infigratinib), the IDH1 inhibitor ivosidenib, HER2-directed regimens (trastuzumab-based therapies and zanidatamab), dabrafenib plus trametinib, zenocutuzumab, and conventional chemotherapy/immunotherapy controls. Most patients had metastatic disease (81.6%), ECOG 0â1 status (87.3%), and prior systemic therapy exposure."

Biomarker • IO biomarker • Metastases • Retrospective data • Review • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • FGFR2 • IDH1 • NRG1

Sex-Stratified Efficacy and Safety of NRG1 Fusion-Directed Therapies in Advanced Cholangiocarcinoma: A Systematic Review and Meta-Analysis With Gender-Based Subgroup Analysis (ACG 2026) - "Six studies comprising 148 patients were included (80 males [54.1%], 68 females [45.9%]). Zenocutuzumab-zbco was administered in 92 patients, afatinib in 34, and other HER2/HER3 agents in 22. Overall pooled ORR was 38.6% (DCR 68.9%), significantly favoring zenocutuzumab (OR 4.12, 95% CI 1.88-9.04)."

Metastases • Retrospective data • Review • Biliary Cancer • Cholangiocarcinoma • Oncology • Pancreatic Adenocarcinoma • Solid Tumor • ERBB3 • HER-2 • NRG1

NRG1 fusions in non-small cell lung cancer: biology, diagnostics, and emerging HER2/HER3 therapies-a narrative review. (PubMed, Transl Lung Cancer Res) - "Other HER2/HER3-targeted strategies, including the bispecific antibody zenocutuzumab and HER3-directed monoclonal antibodies, have shown clinically meaningful antitumor activity...The therapeutic landscape has evolved substantially with the introduction of molecular diagnostics and HER2/HER3-targeted therapies. Continued investigation of resistance mechanisms and optimal treatment sequencing will be crucial to improve outcomes for patients with this rare but clinically impactful disease."

Journal • Review • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • NRG1 • TMB

Efficacy and Tolerability of Zenocutuzumab in Advanced NRG1 Fusion-Positive Cholangiocarcinoma: Results From the eNRGy Phase II Trial. (PubMed, J Clin Oncol) - "Zenocutuzumab demonstrated clinically meaningful and durable antitumor activity with a favorable safety profile in patients with advanced NRG1+ cholangiocarcinoma."

Journal • P2 data • Cholangiocarcinoma • Oncology • Solid Tumor • HER-2 • NRG1

Clinicopathologic Features of NRG1 Fusion-Positive Non-Small Cell Lung Cancer. (PubMed, Genes Chromosomes Cancer) - "Our study demonstrates the histologic and molecular heterogeneity of NRG1 fusion-positive NSCLC, encompassing mucinous and enteric variants of adenocarcinoma. Responses to afatinib were variable, underscoring the need for more effective therapies, including zenocutuzumab and emerging agents."

Clinical • Journal • Retrospective data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD74 • NRG1 • PD-L1

Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer. (PubMed, N Engl J Med) - P2 | "Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion-positive cancer, notably NSCLC and pancreatic cancer, with mainly low-grade adverse events. (Funded by Merus; eNRGy ClinicalTrials.gov number, NCT02912949.)."

Journal • Fatigue • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ERBB3 • HER-2 • NRG1

Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC) (ESMO 2023) - P2 | "No pt discontinued Zeno for a treatment related AE. Conclusions In this updated analysis, Zeno provides robust and durable efficacy in advanced NRG1+ NSCLC, with a well-tolerated safety profile."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD74 • ERBB3 • HER-2 • NRG1 • SLC3A2

Tumor-Agnostic and Histology-Tuned Targeted Therapies in Gastrointestinal Cancers: NTRK and RET Fusions and the Evolving Role of Molecular Basket Strategies. (PubMed, J Gastrointest Cancer) - "In the initial 55-patient larotrectinib analysis, ORR was 75% by independent review and 80% by investigator assessment; the subsequent expanded pooled analysis reported an investigator-assessed ORR of 79%...Mature TRIDENT-1 data support repotrectinib in both TRK inhibitor-naive and pretreated disease, including solvent-front mutations. Selpercatinib received traditional US approval in July 2026, whereas zenocutuzumab provides GI-specific options for NRG1 fusion-positive pancreatic and biliary cancers...Practical implementation requires quantitative prevalence estimates, appropriately selected DNA- and RNA-based testing, recognition of false-positive and false-negative pan-TRK immunohistochemistry, molecular tumor-board interpretation, timely access, and resistance-informed reprofiling. Tumor-agnostic approvals create opportunities, but GI-specific biology determines how reliably and when those opportunities should be used."

Journal • Review • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • MSI • NRG1 • NTRK • RET

Efficacy and safety of zenocutuzumab, a HER2 x HER3 bispecific antibody, across advanced NRG1 fusion (NRG1+) cancers. (ASCO 2022) - P1/2 | "Zeno demonstrated robust and durable efficacy in pts with advanced NRG1+ cancer regardless of tumor histology. A well tolerated safety profile of Zeno was observed."

Clinical • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ATP1B1 • CD74 • ERBB3 • HER-2 • NRG1 • SLC3A2

Cleaning Out Cancer with New Targeted Bile Duct Treatment (Dana-Farber Cancer Institute) - "'Compared to what we typically observe with standard chemotherapy, zenocutuzumab doubles the duration of clinical benefit,' says Cleary, senior author, who published the results in the Journal of Clinical Oncology. 'This is a new option for patients and families who have this alteration.'....'Second-line chemotherapy is only modestly effective for most patients with this disease, and we urgently need better treatment options,' Cleary says. 'Our goal is to develop more effective therapies that can improve quality of life for cholangiocarcinoma patients.'" "

Media quote

The Evolving Role of Bispecific Antibodies in Oncogene-Driven NSCLC. (PubMed, Cancers (Basel)) - "This review summarizes the structural and biological principles underlying bsAb design, with a focus on clinically approved agents such as amivantamab (EGFR/MET) and zenocutuzumab (HER2/HER3) and a growing pipeline of investigational agents...Collectively, available evidence supports a complementary role for bsAbs within evolving multimodal treatment paradigms, particularly in combination strategies. Future directions include biomarker-driven patient selection, improved drug engineering and integration into adaptive therapeutic sequencing frameworks."

Journal • Review • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2 • NRG1

HER2 Therapies in Non-Small Cell Lung Cancer (NSCLC). (PubMed, Int J Mol Sci) - "Concerning treatment, in advanced HER2-positive, Non-Squamous NSCLC tumors, the first-line treatment is Platinum-based + Pemetrexed chemotherapy, with or without immunotherapy, because no HER2-targeted antibody therapy has yet been approved for initial treatment. After progression, HER2-targeted antibody-drug conjugates like Trastuzumab-Deruxtecan and Ado Trastuzumab-Emtansine may offer patients clinical benefits. New HER2-selective tyrosine kinase inhibitors, such as zongertinib and sevabertinib, have shown promising results, including patients previously treated with antibody-drug conjugates (ADCs). Recent advances, including next-generation ADCs such as SHR-A1811 and A166, and bispecific antibodies, such as zenocutuzumab for NRG1 fusion-positive disease, which are also expanding treatment options. Overall, advances in diagnostics and new targeted therapies are changing how HER2-altered NSCLC is treated and are helping to make care more personalized."

IO biomarker • Journal • Review • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NRG1

Dr Bekaii-Saab on the FDA Approval of Zenocutuzumab in NRG1+ Cholangiocarcinoma (OncLive) - "Bekaii-Saab emphasized that with this approval, approximately 30% to 40% of patients with CCA now have an actionable target for treatment...Ultimately, he concluded that identifying these rare but actionable targets is essential for improving outcomes in a disease where precision medicine is increasingly becoming the standard of care.On May 8, 2026, the agent was approved for adult patients with NRG1 fusion–positive advanced, unresectable, or metastatic CCA who have progressed on or after prior systemic therapy. from the phase 1/2 eNRGy trial (NCT02912949), which demonstrated an overall response rate (ORR) of 36.8% (95% CI, 16.3%-61.6%) among 19 evaluable patients per blinded independent central review (BICR). The duration of response (DOR) in the study ranged from 2.8 months to 12.9 months per BICR."

Regulatory • Video

Zenocutuzumab Shows Durable Antitumor Activity in NRG1-Positive Cholangiocarcinoma (THE ASCO POST) - "'Second-line chemotherapy is only modestly effective for most patients with this disease, and we greatly need better treatment options,' said lead study author James M. Cleary, MD, PhD...'Compared to what we typically observe with standard chemotherapy, zenocutuzumab doubles the duration of clinical benefit. In addition, since the therapy is well tolerated, it is a significant step forward in terms of quality of life.'"

Media quote

Partner Therapeutics Announces Publication of Results From the eNRGy Trial of Zenocutuzumab in Patients with NRG1+ Cholangiocarcinoma in Journal of Clinical Oncology (JCO) - "'The FDA approval of zenocutuzumab and the publication of these data represent important progress for patients with NRG1 fusion–positive cholangiocarcinoma. Limited efficacy and poor tolerability of second-line chemotherapy remain a significant clinical challenge in the treatment of patients with advanced cholangiocarcinoma. Zenocutuzumab provided meaningful tumor responses, durable clinical benefit, and a favorable tolerability profile. These findings also underscore the critical importance of comprehensive molecular testing - particularly tissue-based RNA sequencing - to reliably identify NRG1 gene fusions and ensure patients are matched with appropriate targeted therapy.'"

Media quote • Regulatory

Bispecific Antibodies in Solid Tumors: Mechanistic Insights, Clinical Advances, and Future Directions. (PubMed, J Immunother Precis Oncol) - "Recent clinical advancements have led to eight approved bsAbs for solid tumors, including amivantamab for EGFR (epidermal growth factor receptor) exon 20 insertion-mutated non-small cell lung cancer (NSCLC), tebentafusp for uveal melanoma, cadonilimab for cervical cancer, tarlatamab for small cell lung cancer, ivonescimab for PD-L1 (programmed death-ligand 1)-positive NSCLC, zanidatamab for HER2 (human epidermal growth factor receptor 2)-amplified biliary tract cancer, zenocutuzumab for NRG1 (neuregulin 1) fusion-positive tumors, and catumaxomab for malignant ascites...As engineering technologies mature, bsAbs are expected to become integral to precision oncology, expanding safe and effective immunotherapy options for patients with solid tumors. This review aims to provide a comprehensive overview of the mechanisms, clinical applications, challenges, and future directions of bsAbs in solid tumors."

IO biomarker • Journal • Review • Biliary Cancer • Biliary Tract Cancer • Cervical Cancer • Eye Cancer • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Targeted Protein Degradation • Uveal Melanoma • HER-2 • NRG1 • PD-L1

Partner Therapeutics, Inc. (PTx), a private, fully integrated biotechnology company, announced that results from the cholangiocarcinoma cohort of the eNRGy trial (NCT02912949) have been published in the Journal of Clinical Oncology (PRNewswire) - "Data published in JCO include 22 patients with unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma, of whom 19 were evaluable for efficacy...The investigator-assessed overall response rate (ORR), defined as the proportion of patients with tumor shrinkage or disappearance, was 36.8%. Median duration of response was 7.4 months, and median progression-free survival was 9.2 months. The clinical benefit rate was 57.9%, defined as the percentage of patients achieving a complete or partial response or stable disease lasting longer than 6 months. Zenocutuzumab was generally well tolerated."

P2 data • Cholangiocarcinoma

Bispecific antibodies in breast cancer: A systematic landscape analysis of clinical trials. (ASCO 2026) - "Across three phase II HER2-directed BsAb studies, objective response rates ranged 27–76%, with complete responses observed in at least five patients (zenocutuzumab n = 2, KN026 n = 3). The BsAb clinical landscape in breast cancer is rapidly expanding with marked mechanistic heterogeneity and enrichment of HER2-directed strategies. Early outcomes from select agents show meaningful antitumor activity, supporting continued development of oncogene-targeted and immune-modulating BsAbs. Distribution of bispecific antibody clinical trials in breast cancer by target combination and phase."

Bispecific • Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD73 • HER-2 • ICOS • MSLN • TIGIT

Hi-C sequencing to identify clinically actionable fusions in non–small cell lung cancer missed by other sequencing technologies. (ASCO 2026) - "After progression on chemo-immunotherapy, the patient was treated with zenocutuzumab, a recently approved bispecific antibody that blocks NRG1 from activating HER2/HER3 signaling. Hi-C can identify clinically actionable driver alterations in NSCLC cases that were negative on other sequencing tests, highlighting the potential value of incorporating this technology into clinical practice."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • HER-2 • NRG1 • NTRK2

Actionable genomic alterations and survival in KRAS wild-type pancreatic ductal adenocarcinoma: Analysis of the MSK-CHORD 2024 clinico-genomic cohort with spotlight on NRG1 fusions. (ASCO 2026) - "Among these, NRG1 gene fusions have recently gained heightened clinical relevance following the FDA's accelerated approval of zenocutuzumab for NRG1 fusion–positive PDAC after prior therapy... KRAS-WT PDAC accounts for approximately one-tenth of cases and is associated with significantly longer overall survival compared with KRAS-mutant disease. Nearly 1 in 10 KRAS-WT tumors harbored clinically actionable genomic alterations, including NRG1 fusions, now linked to an FDA-approved targeted therapy. These findings support routine comprehensive molecular profiling, including fusion detection, in KRAS-WT PDAC and underscore the clinical relevance of precision oncology approaches in this distinct subgroup."

Microsatellite Instability • Oncology • Pancreatic Ductal Adenocarcinoma • BRAF • BRCA1 • BRCA2 • HER-2 • HRD • KRAS • MSI • NRG1 • NTRK • NTRK1 • NTRK3 • PALB2

FDA Approves Zenocutuzumab for NRG1 Fusion-Positive Cholangiocarcinoma (BioPharm International) - "'NRG1 fusion - positive cholangiocarcinoma represents a rare but clinically important subset of disease with limited therapeutic options and poor outcomes,' said James Cleary, MD, PhD...'These data further highlight the essential role of comprehensive molecular testing, particularly tissue-based RNA-based sequencing, to reliably detect gene fusions such as NRG1 and ensure patients are appropriately identified for targeted therapy.'"

Media quote • Regulatory

FDA approval in cholangiocarcinoma: The FDA has approved zenocutuzumab for NRG1+ Cholangiocarcinoma. @DanaFarber 's @JamesClearyMD helped lead research of the drug in this rare cancer type which has had limited treatment options. ➡️https://bit.ly/4dlQ8vg

Regulatory

Partner Therapeutics…announced that the…FDA has awarded a Commissioner's National Priority Voucher (CNPV) pilot program voucher for BIZENGRI (zenocutuzumab-zbco) for the treatment of adults with advanced, unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy (PRNewswire) - "PTx submitted a supplemental Biologics License Application (sBLA) to the FDA for this indication based on data from the Phase 2 eNRGy trial....The FDA's Commissioner's National Priority Voucher pilot program, announced in June 2025, is designed to reduce drug and biologic review times from the standard 10–12 months to as little as 1–2 months for products that align with one or more U.S. national health priorities."

FDA event • Cholangiocarcinoma

FDA approves zenocutuzumab-zbco for advanced, unresectable or metastatic cholangiocarcinoma (FDA) - "The safety and efficacy of Bizengri were evaluated in eNRGy (NCT02912949), a multicenter, open-label, multi-cohort clinical trial in adults with advanced solid tumors...The recommended zenocutuzumab-zbco dose is 750 mg as an intravenous infusion every two weeks until disease progression or unacceptable toxicity."

FDA approval • Cholangiocarcinoma • NRG1

Neuregulin-1(NRG1)-directed therapies induce alkaline phosphatase placental (ALPP) expression in NRG1-fusion positive cancers: Preclinical data and therapeutic perspective (AACR 2026) - "NRG1+ cancers targeting relies on bispecific anti-ERBB2/ERBB3 antibodies such as zenocutuzumab (zeno) or ERBB2 inhibitors such as afatinib (afa). Afa induced early ALPP expression in NRG1+ MDA-MB-175 cells, and afa-resistance was associated with high ALPP expression and a decrease of ERBB3 and ERK phosphorylation. Validation of ALPP as a relevant target is ongoing using ALPP KO and overexpressing NRG1+ models, including NRG1+ engineered preclinical models and NRG1+ patient-derived models from patients exposed to NRG1-directed therapies. Zeno and zongertinib impact on ALPP expression in preclinical models as well as ALPP expression in a cohort of NRG1+ non-small cell lung cancer and pancreatic ductal adenocarcinoma is ongoing."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ALPP • ERBB3 • NRG1 • TENM4