What Is It, and Why Does It Matter?
Bizengri (zenocutuzumab-zbco) is a prescription intravenous (IV) targeted cancer medicine used to treat certain advanced cancers caused by rare genetic changes (mutations) in the neuregulin 1 (NRG1) gene known as NRG1 gene fusions. The FDA has approved Bizengri for adults with a rare and aggressive NRG1 fusion-positive bile duct cancer (cholangiocarcinoma) that cannot be removed with surgery (is unresectable) or has spread (metastasized) and has worsened after prior treatment.
Cholangiocarcinoma is a rare and aggressive cancer that affects the bile ducts. Fewer than 1% of cholangiocarcinomas have NRG1 gene fusions that produce unique “fusion proteins” (chimeric ligands). These abnormal proteins attach to specific targets (HER2 and HER3) on cancer cells, promoting tumor growth and spread. This makes NRG1-positive cancers fast-growing, aggressive, and difficult to treat with standard treatments. The disease has a poor prognosis, with fewer than 15% of patients surviving beyond 5 years after diagnosis. These patients are often younger adults, and they usually do not have other common cancer-driving mutations that can be treated with existing cancer-targeted medicines. Current chemotherapy treatments can cause significant side effects, and standard second-line treatment options help only a few patients, with response rates of around 5%.
Bizengri is a lab-made bispecific antibody engineered to target two related growth receptors on cells called HER2 and HER3. Bizengri works by blocking the pairing of HER2 and HER3 receptors, preventing the NRG1 fusion proteins from attaching to HER3. This slows down the signaling pathways that drive tumor growth and spread. Additionally, this medicine may also help the body’s immune system to kill cancer cells directly via a process called antibody-dependent cellular cytotoxicity.
Bizengri is also approved for adults with NRG1 fusion‑positive non‑small-cell lung cancer and pancreatic adenocarcinoma that have metastasized or are unresectable and have worsened after prior therapy.
As cancers with NRG1 fusions are very rare and life‑threatening, new treatment options are important when standard treatments are limited. This approval matters because Bizengri is a first-in-class medicine designed to target this rare cancer driver that currently has no approved targeted treatment. The application was reviewed through the FDA Commissioner’s National Priority Review Voucher pilot program and received priority review, both intended to speed up the assessment of medicines that may meet key public health needs.
Why Was It Approved?
The FDA’s approval of Bizengri was based on a clinical trial that showed that this medicine is safe, well tolerated, and effective in producing meaningful tumor responses and lasting benefits in adults with advanced unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma.
In this clinical study involving 19 evaluable patients, 36.8% showed a confirmed tumor response, with responses lasting from 2.8 to 12.9 months, indicating that Bizengri helped shrink tumors in a significant proportion of patients, and the effect lasted for several months.
Safety findings across studies were in line with those for this class of medicine. Common side effects included diarrhea, muscle or joint pain, tiredness, nausea, infusion‑related reactions, shortness of breath, rash, constipation, vomiting, stomach pain, and swelling (edema).
What Do I Need to Know?
You need confirmation that your tumor has an NRG1 gene fusion to receive Bizengri. As an FDA‑approved test for this is not available, your health care team will use a reliable and validated method to confirm your eligibility to receive this treatment.
You will receive Bizengri as an IV infusion every two weeks under medical supervision, and each infusion takes about four hours. You will be kept under observation for at least one hour after your first dose. Your health care provider may also give you certain medicines before starting the infusion to minimize infusion-related reactions.
Your health care provider will stop your treatment immediately and permanently if you experience life‑threatening infusion-related or hypersensitivity reactions or develop serious lung inflammation (interstitial lung disease [ILD] or pneumonitis) or congestive heart failure.
As Bizengri can affect heart function, your health care provider will check your heart’s pumping strength (left ventricular ejection fraction) before starting and during your treatment. If interstitial ILD is suspected, your health care team will pause therapy and may give steroids, depending on severity.
Before starting Bizengri, tell your health care provider if you are allergic to it or to any of its ingredients or have any heart or lung problems, and about other details of your medical history.
Inform your health care provider about all the medicines, including over-the-counter products, herbal remedies, and vitamin supplements, that you take.
Bizengri can harm a fetus. Your health care provider will check your pregnancy status before starting your treatment. If you can become pregnant, use effective birth control during the therapy and for two months after the last dose. Do not breastfeed during treatment or for two months after the final dose.
Call your health care provider right away if you have symptoms that suggest an infusion reaction, such as fever, chills, nausea, or cough. Also report new or worse breathing problems, like shortness of breath, cough, or fever, which could be signs of lung inflammation or ILD.