FDA Grants Fast Track Designation to Zenocutuzumab for Metastatic NRG1+ Solid Tumors

The FDA has granted a fast track designation to zenocutuzumab (Zeno; MCLA-128) for the treatment of patients with metastatic solid tumors that harbor NRG1 gene fusions and have progressed on standard-of-care treatment, according to an announcement from Merus NV, the drug developer.¹

“Receiving fast track designation is another important milestone for Zeno, and it validates the potential for addressing the unmet need of patients with NRG1+ cancers,” Andrew Joe, MD, chief medical officer of Merus NV, stated in a press release. 

In the open-label, multicenter, multinational, dose-escalation, phase 1/2 eNRGy trial (NCT02912949), investigators are examining the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of zenocutuzumab in patients with NRG1 fusion–positive solid tumors.² 

To be eligible for enrollment, patients need to have at least 1 measurable lesion per RECIST v1.2 criteria, an ECOG performance status of 0 or 1, and an estimated life expectancy of 12 weeks, among other criteria. If they are pregnant or lactating, have an active uncontrolled infection or unexplained fever, known hypersensitivity to any of the components of the study drug, or have known symptomatic or unstable brain metastases, they will be excluded from the research.

The first-in-human study is comprised of 2 parts; part 1 is the dose-escalation portion of the research, while part 2 will be the expansion cohort. The part 2 portion of the research will include 2 new patient populations: group F will comprise patients with non–small cell lung cancer that harbors a NGR1 fusion, group G will include those with NRG1 fusion–positive pancreatic cancer, and group H will include those with any other NRG1 fusion–positive solid tumor.

In the new populations, investigators will work to further characterize the safety and tolerability of zenocutuzumab at the dose level selected in part 1, as well as evaluate the clinical benefit rate of the drug. Overall response rate (ORR) and duration of response (DOR) will be assessed and reported in these new populations, as well.

The trial will be conducted in 3 parts: a screening period, which will take place 28 days before the first dose of the drug is administrated; a treatment period, which will be done in cycles of 28 days, and a follow-up period, which will take place 30 days following the last dose of zenocutuzumab and will include quarterly checks for survival information for up to 2 years.

Across the different groups examined, zenocutuzumab will be administered via an intravenous infusion at a dose of 750 mg, which was established as the recommended phase 2 dose for the agent.

The primary outcome measures of the trial included characterization of safety and tolerability of zenocutuzumab, ORR, and DOR, as well as correlation of antitumor activity and biomarkers of HER2, HER3, Heregulin, and disease-related biomarkers.

“We continue to add clinical trial sites to and enroll patients in the eNRGy trial and look forward to providing a substantial clinical program update at a major medical meeting in the second quarter of 2021,” Joe added in the release.

References

1. Merus granted FDA fast track designation of zenocutuzumab for the treatment of patients with Neuregulin 1 Fusion cancers. News release. Merus NV. January 7, 2021. Accessed January 8, 2021. http://bit.ly/3bobmtY.
2. A study of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion. ClinicalTrials.gov. Updated October 30, 2020. Accessed January 8, 2021. https://clinicaltrials.gov/ct2/show/NCT02912949.