On December 4, 2024, the Food and Drug Administration granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for use in adults with specific conditions.
Patients with advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) exhibiting a neuregulin 1 (NRG1) gene fusion and experiencing disease progression following prior systemic therapy, or those with advanced, unresectable, or metastatic pancreatic adenocarcinoma with an NRG1 gene fusion and disease progression after prior systemic therapy.
This marks the inaugural FDA approval of a systemic therapy for patients with non-small cell lung cancer (NSCLC) or pancreatic adenocarcinoma that possess an NRG1 gene fusion.
The efficacy was assessed in the eNRGy study (NCT02912949), a multicenter, open-label, multicohort trial. The trial included 64 adults with advanced or metastatic NRG1 fusion-positive non-small cell lung cancer (NSCLC) and 30 adults with advanced or metastatic NRG1 fusion-positive pancreatic adenocarcinoma, all of whom experienced disease progression after standard care treatment. The positive NRG1 gene fusion status was prospectively identified using next-generation sequencing assays.
The primary efficacy outcome measures included the overall response rate (ORR) and duration of response (DOR), assessed through blinded independent central review in accordance with RECIST v1.1 guidelines. The overall response rate (ORR) for non-small cell lung cancer (NSCLC) was 33% (95% confidence interval: 22%, 46%), with a median duration of response (DOR) of 7.4 months (95% confidence interval: 4.0, 16.6). In pancreatic adenocarcinoma, the objective response rate (ORR) was 40% (95% confidence interval: 23%, 59%), with a duration of response (DOR) ranging from 3.7 months to 16.6 months.
The pooled safety population revealed that the most prevalent adverse reactions (≥10%) included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. The predominant Grade 3 or 4 laboratory abnormalities (≥10%) included elevated gamma-glutamyl transferase, reduced hemoglobin, diminished sodium levels, and decreased platelet counts. The prescribing information contains a boxed warning regarding embryo-fetal toxicity.
The advised dosage of zenocutuzumab-zbco is 750 mg, administered as an intravenous infusion biweekly, continuing until disease progression or intolerable toxicity occurs.
Susan Hau is a distinguished researcher in the field of cancer cell therapy, with a particular focus on T cell-based approaches and cancer vaccines. Her work spans several innovative treatment modalities, including CAR T-cell therapy, TIL (Tumor-Infiltrating Lymphocyte) therapy, and NK (Natural Killer) cell therapy.
Hau's expertise lies in cancer cell biology, where she has made significant contributions to understanding the complex interactions between immune cells and tumors.
Her research aims to enhance the efficacy of immunotherapies by manipulating the tumor microenvironment and exploring novel ways to activate and direct immune responses against cancer cells.
Throughout her career, Hau has collaborated with leading professors and researchers in the field of cancer treatment, both in the United States and China.
These international experiences have broadened her perspective and contributed to her innovative approach to cancer therapy development.
Hau's work is particularly focused on addressing the challenges of treating advanced and metastatic cancers. She has been involved in clinical trials evaluating the safety and efficacy of various immunotherapy approaches, including the promising Gamma Delta T cell therapy.
