LEXINGTON, Mass., Oct. 23, 2025 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to zenocutuzumab-zbco for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion. The designation was supported by results from the ongoing investigational Phase 2 eNRGy trial. These findings will be presented as both an oral and poster presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, MA and will serve as the basis for a supplemental Biologics License Application (sBLA) that will be submitted to FDA in 2026.
BTD is granted by the FDA to expedite the development and review of therapies that may demonstrate substantial improvement over existing treatments for serious or life-threatening conditions. The designation conveys all of the fast track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment, and eligibility for rolling review and priority review. For adult patients with advanced unresectable or metastatic NRG1+ cholangiocarcinoma, a rare and aggressive cancer with limited treatment options, this designation underscores the urgent need for effective therapies and recognizes the potential of zenocutuzumab-zbco to help address this significant unmet medical need.
The designation was supported by new interim data presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics meeting which evaluated zenocutuzumab-zbco in patients with advanced NRG1+ cholangiocarcinoma in the eNRGy trial. In 19 evaluable patients, the results demonstrated an investigator-assessed overall response rate of 37%, a median duration of response of 7.4 months, and a median time to response of 1.9 months. Progression-free survival was 9.2 months and clinical benefit rate, defined as partial/complete response or stable disease for ≥24 weeks, was 58%. Among patients with evaluable CA 19-9 data, all experienced a decline in serum levels, including a >50% reduction in 69% of patients. The safety profile was consistent with the overall eNRGy trial population, with most adverse events grade 1 or 2. Five patients (23%) experienced serious adverse events, none considered treatment related, and no patients discontinued therapy due to treatment-related toxicity.
Dr. Alison M. Schram, Principal Investigator of the eNRGy trial and medical oncologist from Memorial Sloan Kettering Cancer Center, commented: "NRG1 fusions represent a rare but actionable driver in cholangiocarcinoma, and the data from the eNRGy trial continue to highlight the potential of zenocutuzumab to offer meaningful clinical benefit for these patients. I'm honored to present these findings at AACR-NCI-EORTC, where we can advance the dialogue around targeted therapies in hard-to-treat cancers."
"Patients with cholangiocarcinoma face an aggressive disease with limited standard therapy options," said Juan W. Valle, MD, Chief Medical Officer of the Cholangiocarcinoma Foundation. "The eNRGy trial results are encouraging, and they underscore how critical comprehensive molecular testing, notably tissue-based RNA NGS, is to ensure that patients with rare drivers such as NRG1 fusions are identified and can potentially have access to targeted treatments."
"In December 2024, zenocutuzumab-zbco (tradename BIZENGRI) received accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The new data from the eNRGy trial highlight the potential of zenocutuzumab-zbco as a promising treatment option for patients with NRG1 fusion–positive cholangiocarcinoma," said Pritesh J. Gandhi, PharmD, Chief Development Officer of Partner Therapeutics. "With the growing number of genomic alternations and gene fusions that are now actionable, it is imperative that oncologists order upfront tissue-based RNA next generation sequencing to ensure that gene fusions, of which NRG1 is just one, are not missed."
A copy of the poster and presentation will be available on the Partner Therapeutics website under the research tab following the conference. Additional meeting information can be found on the AACR-NCI-EORTC website.
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).
For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.
Dr. Schram has financial interests related to Partner Therapeutics.
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 tissue-based 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%).
Please see full Prescribing Information, including Boxed Warning
About Partner Therapeutics
Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of therapeutics to improve health outcomes in cancer and serious diseases, as well as global health security threats. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. PTx's portfolio includes sargramostim (EU: IMREPLYS®; US: LEUKINE®; and with Nobelpharma Co. Ltd for JAPAN: SARGMALIN®) and zenocutuzumab-zbco . Visit www.partnertx.com.
References:
BIZENGRI® is a registered trademark of Merus N.V. under an agreement with Merus, PTx has exclusive rights to develop, manufacture, and commercialize zenocutuzumab-zbco for the treatment of NRG1+ cancer in the U.S. and provide the product on a named-patient basis for this use outside of the U.S. pending future regulatory developments.
PARTNER THERAPEUTICS®, IMREPLYS®, and LEUKINE® are registered trademarks owned by Partner Therapeutics, Inc.
©2025 Partner Therapeutics, All rights reserved.
SOURCE Partner Therapeutics, Inc.
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