Trial Supports Bizengri as a Promising Treatment for NRG1 Fusion-Positive Cancers, Including Advanced Lung Cancer

New research, published in the New England Journal of Medicine in February 2025, adds support for the safety and efficacy of Bizengri (zenocutuzumab), a bispecific antibody drug, in patients with advanced NRG1 fusion–positive cancers.

Merus’ Bizengri received accelerated FDA approval in December 2024 to treat patients with advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion in adults whose cancer has progressed during or after previous treatment.

The approval was based on results from the eNRGy study, an open-label trial involving 94 adults with either NRG1 fusion–positive NSCLC or pancreatic cancer who experienced progression after standard treatments. The results showed a 33% overall response rate (ORR) for NSCLC and a 40% ORR for pancreatic cancer, with duration of response between 3.7 and 16.6 months.

NRG1 is a protein normally involved in tissue development, but when its gene rearranges and forms fusions with other genes, it can promote cancer growth. These fusions occur in less than 1% of solid tumors, but they are more common in invasive adenocarcinomas of the lung and pancreas.

Bizengri is a bispecific antibody that targets two proteins, HER2 and HER3, on cancer cell surfaces. When these proteins become overactive in cancer, they bind together, sending signals that lead to uncontrolled cell growth. Bizengri works by blocking this pairing and preventing the NRG1 fusion proteins from binding to HER3, stopping the cancer cells from receiving growth signals. By targeting the interactions between HER2, HER3, and NRG1 fusion proteins, Bizengri offers a promising treatment for these cancers.

Alison M. Schram, M.D.

Now, a group of researchers, led by Alison M. Schram, M.D., oncologist and early drug development specialist at the Memorial Sloan Kettering Cancer Center in New York, have published the results of a larger phase 2 clinical study evaluating the drug’s efficacy and safety in a diverse group of patients with NRG1 fusion-positive solid tumors.

“This study is the first prospective trial to validate NRG1 fusions as a targetable oncogenic driver in cancer,” Schram told MHE in an email. “It is also the first to validate an oncogenic ligand as a target.”

The study involved 204 patients with advanced cancer, including 12 tumor types, who were treated with Bizengri at a dosage of 750 mg intravenously every two weeks. The results revealed that 30% of patients with measurable disease had a response to the treatment, with a median duration of 11.1 months.

Notably, responses were observed in several cancer types, including 29% of patients with NSCLC and 42% of patients with pancreatic cancer. The median progression-free survival for all participants was 6.8 months.

“These results are particularly exciting because NRG1+ lung cancers typically do not respond to standard chemotherapy or immunotherapy, and there are no approved targeted treatments for this patient population,” Schram stated in a press release.

In terms of safety, adverse events were mostly mild, with diarrhea, fatigue, and nausea being the most common side effects. Infusion-related reactions were noted in 14% of patients, and only one patient discontinued the treatment due to a treatment-related adverse event.

“Based on the impressive efficacy of zenocutuzumab [Bizengri] in non-small cell lung cancer and pancreatic cancer, zenocutuzumab was FDA approved for these patient populations,” Schram said. “These are both diseases that are in significant need of better therapies, and zenocutuzumab offers an exciting and promising new option for patients with NRG1 fusion-positive lung and pancreatic cancer."