FDA to Consider Zenocutuzumab in NRG1+ NSCLC and Pancreatic Cancer


If approved, zenocutuzumab would be the first targeted therapy for neuregulin 1 fusion-positive lung and pancreatic cancers.

Cluster of tumors cells: © Yuriy - stock.adobe.com

Cluster of tumors cells: © Yuriy - stock.adobe.com

  • The FDA has granted priority review to the biologics license application (BLA) of zenocutuzumab (MCLA-128) in patients with neuregulin 1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC).
  • With this priority review, the FDA aims to act on the BLA within 6 months compared with 10 months under standard review.
  • The BLA is supported by the phase 1/2 eNRGy trial (NCT02912949).

The FDA has accepted and given priority review to the BLA of zenocutuzumab, a bispecific antibody for the treatment of NRG1+ NSCLC and PDAC.1 With this priority review, the FDA plans to review and decide on the BLA within 6 months.

“FDA acceptance of our first BLA represents an important achievement for Merus and an important potential treatment opportunity for patients with NRG1+ cancer, a disease with poor prognosis and high unmet need,” said Andrew Joe, MD, chief medical officer at Merus, in a press release. “Zenocutuzumab has the potential to be the first and only targeted therapy for patients with NRG1+ lung and pancreatic cancer and may offer a substantial improvement over currently available therapies.”

The phase 1/2 eNRGy trial investigating the safety and antitumor activity of zenocutuzumab supports this BLA filing. Data from this trial were presented at the American Society of Clinical Oncology Annual Meeting in 2021 and 2022 as well as at the European Society for Medical Oncology (ESMO) 2023 Congress.

The FDA previously granted breakthrough therapy designation to zenocutuzumab for the treatment of patients with advanced unresectable or metastatic NRG1+ PDAC and NSCLC following progression on systemic therapy.

Zenocutuzumab delivered an overall response rate (ORR) of 37.2% (95% CI, 26.5%-48.9%) and a clinical benefit rate (CBR) of 61.5% (95% CI, 49.8%-72.3%) in patients with NRG1+ NSCLC, according to data presented at the 2023 ESMO Congress.2

About the Phase 1/2 eNRGy Trial

eNRGy is an open-label, multicenter, dose-escalation study of zenocutuzumab in patients with solid tumors with a NRG1 fusion.3 The study has an estimated enrollment of 250 patients. The primary end points are ORR and duration of response, and secondary end points include CBR, time to response, safety, tolerability, pharmacokinetics, overall survival, and progression-free survival.

Patients with at least 1 measurable lesion, an ECOG performance status of 0 to 2, an estimated life expectancy of at least 12 weeks, resolved toxicities from prior therapies, and adequate laboratory levels are eligible for participation in the trial. Patients who are pregnant or lactating, have a known HIV or hepatitis infection, have leptomeningeal metastases, or a previous or concurrent malignancy are not eligible for enrollment in the study.

1. Merus Announces U.S. FDA acceptance and priority review of biologics license application for Zeno for the treatment of NRG1+ NSCLC and PDAC. News release. Merus. May 6, 2024. Accessed May 7, 2024. https://tinyurl.com/3cs8bc2r
2. Schram A, Goto K, Kim D, et al. Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positivive (NRG1+) non-small cell lung cancer (NSCLC). Presented at: 2023 European Society for Medical Oncology Congress. October 20-24, 2023. Madrid, Spain. Abstract 1215MO.
3. A study of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion (eNRGy). ClinicalTrials.gov. Updated January 17, 2024. Accessed May 7, 2024. https://clinicaltrials.gov/study/NCT02912949
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