On April 14, 2026 Partner Therapeutics, Inc. (PTx), a private, fully integrated biotechnology company, reported the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for BIZENGRI (zenocutuzumab-zbco), seeking approval for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion. Cholangiocarcinoma is a rare, aggressive malignancy of the bile ducts with few effective treatment options. There are no approved therapies specifically targeting cholangiocarcinoma harboring NRG1 gene fusions.
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"This submission marks an important step in advancing BIZENGRI for patients with NRG1 fusion positive cholangiocarcinoma, a population with limited treatment options, and historically poor outcomes. Cholangiocarcinoma remains a challenging and aggressive disease, and we believe these data support the potential of BIZENGRI to address a critical unmet need for patients whose tumors are driven by NRG1 gene fusions. Tissue‑based RNA testing is essential to identify rare oncogenic fusions such as NRG1 and ensure patients with these actionable alterations are not overlooked," said Pritesh J. Gandhi, Chief Development Officer, Partner Therapeutics.
The sBLA is supported by data from the eNRGy study evaluating zenocutuzumab-zbco in patients with NRG1 fusion-positive cancers, including cholangiocarcinoma. In the cholangiocarcinoma cohort, BIZENGRI demonstrated an overall response rate (ORR) of 36.8% (95% CI: 16.3, 61.6%) and a median duration of response (DOR) of 12.9 months, as assessed by blinded independent central review (BICR). Treatment was generally well tolerated, and no patients discontinued therapy due to adverse events.
Based on these data, National Comprehensive Cancer Network (NCCN) added zenocutuzumab‑zbco to the Oncology Clinical Practice Guidelines for biliary tract cancers as a Category 2A subsequent‑line therapy and as a Category 2B recommendation for front‑line treatment of NRG1 fusion–positive cholangiocarcinoma.
"Cholangiocarcinoma remains a devastating disease, particularly in the advanced setting. The identification of NRG1 gene fusions has highlighted an actionable biomarker, and the eNRGy study data suggest that targeted inhibition with zenocutuzumab may represent a meaningful treatment approach for these patients" said Dr. James Cleary, Dana-Farber Cancer Institute.
BIZENGRI received U.S. Food and Drug Administration accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer and pancreatic adenocarcinoma harboring NRG1 gene fusions with disease progression on or after prior systemic therapy.
For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.
National Comprehensive Cancer Network
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
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 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization 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.
About BIZENGRI (zenocutuzumab-zbco)
INDICATIONS
BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.
BIZENGRI is indicated for the 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.
These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Important Safety Information
BOXED WARNING: EMBRYO-FETAL TOXICITY
Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.
WARNINGS AND PRECUATIONS
Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions
BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.
In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.
Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.
Interstitial Lung Disease/Pneumonitis
BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis.
In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated.
Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed.
Left Ventricular Dysfunction
BIZENGRI can cause left ventricular dysfunction.
Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.
In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.
Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI.
Embryo-Fetal Toxicity
Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.
ADVERSE REACTIONS
NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC
Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each).
In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).
NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma
Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI.
There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure.
In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).
(Press release, Partner Therapeutics, APR 14, 2026, View Source [SID1234664367])