The FDA has granted accelerated approval to Bizengri (zenocutuzumab-zbco) for the treatment of adult patients with advanced unresectable or metastatic pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) whose tumors harbor a neuregulin 1 (NRG1) gene fusion and have progressed on or after prior systemic therapy. This marks a significant advancement as Bizengri is the first systemic therapy approved by the FDA to specifically target NRG1 gene fusions in these cancers. The approval was primarily based on data from the eNRGy trial (NCT02912949), highlighting the drug's efficacy and safety profile. Alison Schram, MD, from Memorial Sloan Kettering Cancer Center, a lead investigator in the eNRGy trial, noted that this approval is an important milestone, as she has seen firsthand how Bizengri can deliver clinically meaningful outcomes for patients.
Targeting NRG1 Fusions
NRG1 fusions are genetic alterations present in a small percentage of solid tumors, including pancreatic and lung cancers. These fusions result in the overproduction or malfunction of the NRG1 growth factor, leading to uncontrolled tumor cell growth via the HER3 protein receptor. Bizengri, a bispecific antibody, targets both HER2 and HER3, effectively blocking NRG1 signaling and inhibiting tumor growth. This mechanism is particularly relevant as these tumors often do not respond well to standard treatment options.
Clinical Efficacy and Safety
The FDA's decision was influenced by the eNRGy trial, an open-label Phase 2 clinical trial involving 30 adults with NRG1 fusion-positive pancreatic adenocarcinoma and 64 adults with NRG1 fusion-positive NSCLC. All patients had experienced disease progression following standard of care treatments. The primary goal was to measure the overall response rate (ORR) and duration of response (DOR).
In the pancreatic cancer cohort, the ORR was 40%, with a DOR ranging from 3.7 to 16.6 months. The NSCLC cohort showed an ORR of 33% and a median DOR of 7.4 months (95% CI, 4.0-16.6). These results underscore the potential of Bizengri to provide clinically meaningful benefits in these difficult-to-treat cancers.
The most common side effects reported during clinical testing included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. A boxed warning highlights the potential harm to a developing fetus during pregnancy. The recommended dose is 750 mg administered intravenously every two weeks until disease progression or unacceptable side effects occur.
Personalized Medicine and Future Implications
Edward Abrahams, PhD, president of the Personalized Medicine Coalition, emphasized that Bizengri offers the only approved NRG1+ therapy for these difficult-to-treat cancers, aligning with the growing trend of personalized medicines. This approval underscores the importance of biomarker testing to identify NRG1 fusions, enabling targeted treatment strategies. Merus has partnered with Partner Therapeutics for the U.S. commercialization of Bizengri, ensuring patient access and support through programs like PTx Assist™.
Shannon Campbell, Chief Commercial Officer of Merus, stated that this approval is a testament to their technology and strong execution as they continue to develop their multispecific platforms and pipeline.
