Zenocutuzumab

BIZENGRI® is a bispecific HER2- and HER3-directed antibody 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.*. Adults with advanced, unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 ( NRG1 ) gene fusion with disease progression on or after prior systemic therapy.*. 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).

Zenocutuzumab-zbco is a bispecific antibody that binds to the extracellular domains of HER2 and HER3 expressed on the surface of cells, including tumor cells, inhibiting HER2:HER3 dimerization and preventing NRG1 binding to HER3. Zenocutuzumab-zbco decreased cell proliferation and signaling through the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway. In addition, zenocutuzumab-zbco mediates antibody-dependent cellular cytotoxicity (ADCC). Zenocutuzumab-zbco showed antitumor activity in mouse models of NRG1 fusion-positive lung and pancreatic cancers.

Select patients for treatment with BIZENGRI based on the presence of an NRG1 gene fusion. Evaluate left ventricular ejection fraction (LVEF) before initiating BIZENGRI. The recommended dosage of BIZENGRI is 750 mg every 2 weeks until disease progression or unacceptable toxicity. Administer premedications before each infusion to reduce the risk of infusion-related reactions. Administer as an intravenous infusion, after dilution, over 4 hours.

None. None.

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. Infusion-Related Reactions (IRR)/Hypersensitivity/Anaphylactic Reactions: Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor for signs and symptoms of IRR. Interrupt 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. Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis.

The following clinically significant adverse reactions are described elsewhere in the labeling: Infusion-Related Reactions/Hypersensitivity/Anaphylaxis Interstitial Lung Disease/Pneumonitis Left Ventricular Dysfunction Embryo-Fetal Toxicity The most common adverse reactions (≥ 10%) in patients were diarrhea musculoskeletal pain, fatigue, nausea, infusion-related reactions (IRR), dyspnea, rash, constipation, vomiting, abdominal pain, and edema. The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were increased GGT, decreased hemoglobin, decreased sodium, decreased platelets, increased AST, increased ALT, increased alkaline phosphatase, decreased magnesium, decreased phosphate, increased aPTT and increased bilirubin.

Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.