On Dec. 4, the U.S. Food and Drug Administration (FDA) granted accelerated approval to zenocutuzumab-zbco (Bizengri) for adults with NRG1-positive non-small cell lung cancer (NSCLC) or pancreatic adenocarcinoma who meet certain criteria.
The approval indicates zenocutuzumab, a HER2 × HER3 bispecific antibody, for adults with advanced, unresectable, or metastatic NSCLC harboring NRG1 gene fusion with disease progression on or after prior systemic therapy and for adults with NRG1-positive pancreatic adenocarcinoma who have progressed after prior systemic therapy. This is the first approval of a systemic therapy for patients with NRG1-positive NSCLC or pancreatic adenocarcinoma.
Regulators based their decision on the results of the multicenter, open-label, multicohort, eNRGy clinical trial. The phase 1/2 study included 64 adults with advanced or metastatic NRG1 fusion–positive NSCLC and 30 adults with advanced or metastatic NRG1 fusion–positive pancreatic adenocarcinoma. All patients experienced disease progression after receiving standard-of-care treatment. Researchers determined NRG1 gene fusion status prospectively through next-generation sequencing assays.
The study’s primary endpoints were overall response rate (ORR) and duration of response (DOR). A blinded independent central review determined these results using RECIST v1.1 criteria.
For patients with NSCLC, the ORR was 33% (95% confidence interval [CI], 22%–46%) and the median DOR was 7.4 months (95% CI, 4.0–16.6 months). Among patients with pancreatic adenocarcinoma, the ORR was 40% (95% CI, 23%–59%) and the DOR range was 3.7–16.6 months.
“The FDA approval of Bizengri marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion. I have seen firsthand how treatment with Bizengri can deliver clinically meaningful outcomes for patients,” said Alison Schram, MD, a principal investigator for the eNRGy trial and an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center in New York City, in a news release from Merus N.V, the drug’s manufacturer. “I am extraordinarily grateful for the patients and families who participated in the trial.”
According to pooled safety data, the most common adverse reactions, which occurred in at least 10% of patients, included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema.
The most common grade 3 or 4 laboratory abnormalities, which occurred in at least 10% of patients, included increased gamma-glutamyl transferase, decreased hemoglobin, decreased sodium, and decreased platelets. The FDA also included a Boxed Warning for embryo-fetal toxicity.
The recommended dose for zenocutuzumab is 750 mg every two weeks via an intravenous infusion. It can be administered until the occurrence of disease progression or unacceptable toxicity.
