On May 11, 2026 Partner Therapeutics, Inc. (PTx), a private, fully integrated biotechnology company, reported that the U.S. Food and Drug Administration (FDA) has approved 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. This marks the first targeted therapy approved specifically for NRG1+ cholangiocarcinoma, a molecularly defined cancer with a profound unmet need. The approval was expedited by PTx’s receipt of a Commissioner’s National Priority Voucher (CNPV). BIZENGRI previously received Breakthrough Therapy Designation and Orphan Drug Designation from the FDA for NRG1+ cholangiocarcinoma, reflecting the unmet need in this patient population.
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"Today’s FDA approval of BIZENGRI for NRG1 fusion-positive cholangiocarcinoma is a historic milestone for patients who have had no approved targeted therapy. We thank the patients, their families, and the investigators for their participation in the eNRGy trial. The results demonstrate meaningful tumor responses, durable benefit, and a favorable tolerability profile—and we are grateful that the FDA’s Commissioner’s National Priority Voucher pilot program greatly reduced the review time, helping bring this treatment to patients more quickly. We look forward to working with the oncology community to ensure appropriate patients can access BIZENGRI without delay."
— Pritesh J. Gandhi, Chief Development Officer, Partner Therapeutics
FDA APPROVAL FOR NRG1+ CHOLANGIOCARCINOMA
The FDA approved BIZENGRI based on safety and efficacy data from the eNRGy trial, a multicenter, open-label, multi-cohort Phase 2 clinical trial in adults with advanced solid tumors harboring NRG1 gene fusions. A total of 22 patients with unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma were enrolled, with 19 evaluable for efficacy.
The major efficacy outcome measures were confirmed overall response rate (ORR), which is the percentage of patients in a clinical trial whose cancer shrinks or disappears after treatment, and duration of response (DOR). The ORR was 36.8% with a DOR range of 2.8 to 12.9 months.
The most common adverse reactions (≥20%), excluding laboratory findings, were fatigue, diarrhea, musculoskeletal pain, abdominal pain, nausea, cough, dyspnea, and decreased appetite.
"NRG1 fusion–positive cholangiocarcinoma represents a rare but clinically important subset of disease with limited therapeutic options and poor outcomes. In the eNRGy study, zenocutuzumab demonstrated a clinically meaningful overall response rate, and the drug was well tolerated with a favorable safety profile. Less than 1% of patients discontinued treatment due to a drug related adverse event, supporting its role as a targeted treatment option in this setting. 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."
— James Cleary, MD, PhD, Director of Clinical Research, Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School
BIZENGRI was first approved under accelerated approval in 2024 in advanced, unresectable or metastatic non-small cell lung cancer and pancreatic adenocarcinoma for patients harboring an NRG1 gene fusion on or after systemic therapy. Additionally, zenocutuzumab is included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for non-small cell lung cancer, pancreatic adenocarcinoma, and cholangiocarcinoma.
For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.
About NRG1+ Cholangiocarcinoma
Cholangiocarcinoma is a rare, aggressive malignancy of the bile ducts with an all-stage 5-year overall survival of less than 15%. NRG1 gene fusions occur in fewer than 1% of cholangiocarcinoma cases. NRG1 fusions typically occur in patients who are otherwise driver negative, leaving affected patients, many of whom are younger adults, without approved targeted therapy. Standard cytotoxic regimens carry substantial toxicity, and second-line options such as FOLFOX produce objective responses in only approximately 5% of patients.
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.*
BIZENGRI is indicated 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.
*This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication 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 PRECAUTIONS
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 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 transferase (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 transferase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).
NRG1 Gene Fusion Positive Advanced, Unresectable or Metastatic Cholangiocarcinoma
Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive cholangiocarcinoma who received BIZENGRI (n=22).
In patients with NRG1 gene fusion positive cholangiocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased magnesium (59%), increased alanine aminotransferase (50%), fatigue (46%), decreased platelets (46%), decreased hemoglobin (41%), increased aspartate aminotransferase (41%), increased alkaline phosphatase (41%), decreased phosphate (41%), diarrhea (41%), abdominal pain (36%), musculoskeletal pain (36%), increased gamma-glutamyl transferase (36%), increased bilirubin (32%), decreased potassium (32%), decreased sodium (32%), nausea (27%), cough (27%), increased activated partial thromboplastin time (aPTT) (27%), dyspnea (23%), decreased appetite (23%), and decreased albumin (23%).
(Press release, Partner Therapeutics, MAY 11, 2026, View Source [SID1234665458])