- BIZENGRI® is the first and only FDA-approved therapy specifically for patients with advanced unresectable or metastatic pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) who harbor NRG1 gene fusions1
- NRG1 gene fusions are best detected by tissue-based RNA next generation sequencing (NGS)3
LEXINGTON, Mass., Feb. 5, 2025 -- Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company announced today that the New England Journal of Medicine (NEJM) published results of the 204-patient, global, multicenter, single-arm, Phase 2 clinical trial of zenocutuzumab-zbco (BIZENGRI®) (eNRGy trial; NCT02912949).2 The eNRGy trial evaluated overall response rate to zenocutuzumab-zbco in patients with NRG1 gene fusions across multiple tumor types. Responses by tumor type and safety data are detailed in the NEJM manuscript.
New England Journal of Medicine Publishes eNRGy Trial Evaluating Zenocutuzumab-zbco (BIZENGRI®) in NRG1+ cancer
"Zenocutuzumab helps fill an important need for patients with advanced pancreatic cancer and NSCLC with NRG1 gene fusions," said Alison Schram M.D., an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, a principal investigator for the eNRGy trial, and lead author on the NEJM manuscript. "The overall response rate and durability of responses we observed in the eNRGy trial are noteworthy. I strongly encourage my colleagues to obtain tissue-based RNA NGS to identify NRG1 rearrangements and other oncogenic gene alterations, particularly in otherwise driver-negative tumors, as fusions often are missed by DNA-based NGS techniques."
"The eNRGy study highlights that NRG1 fusions are an actionable therapeutic target and the importance of developing biomarker driven therapies like zenocutuzumab," said Debasish Roychowdhury, MD, Chief Technology Officer at PTx. "We are deeply grateful to the Merus team that designed, researched and developed zenocutuzumab, the eNRGy trial investigators, and the dedicated study participants who helped advance this important research."
A subset of data from the eNRGy trial reported in the NEJM publication supported the recent FDA approval of BIZENGRI in adult patients with pancreatic adenocarcinoma or NSCLC that are advanced unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have disease progression on or after prior systemic therapy. These indications are approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). BIZENGRI® has a Boxed WARNING for Embryo-Fetal Toxicity and warnings for infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions, interstitial lung disease (ILD)/pneumonitis, and left ventricular dysfunction.1 See Important Safety Information below.
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. The companies are working to provide BIZENGRI for commercial distribution as quickly as possible.
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 activating 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.
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 postmarketing 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 other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit the PTx website and LinkedIn.
References:
- BIZENGRI® (zenocutuzumab-zbco) injection [package insert]. Available at: https://www.bizengri.com/pi
- Schram AM, Goto K, Kim DW, et al. Efficacy of Zenocutuzumab in NRG1 Fusion–Positive Cancer. N Engl J Med. 2025;392:566-76. doi: 10.1056/NEJMoa2405008
- Drilon A, Duruisseaux M, Han JY, et al. Clinicopathologic Features and Response to Therapy of NRG1 Fusion-Driven Lung Cancers: The eNRGy1 Global Multicenter Registry. J Clin Oncol. 2021;39(25):2791-2802. doi:10.1200/JCO.20.03307
BIZENGRI® is a registered trademark of Merus N.V.
PARTNER THERAPEUTICS® is a registered trademark owned by Partner Therapeutics, Inc.
©2025 Partner Therapeutics, All rights reserved.
Investor and Media Inquiries:
Partner Therapeutics Media Relations
781-786-2405
media.relations@partnertx.com
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