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

The FDA has granted a Fast Track designation to zenocutuzumab (MCLA-128) as a potential treatment option for patients with metastatic solid tumors harboring NRG1 gene fusions that have progressed on standard of care therapy.

“Receiving Fast Track designation is another important milestone for zenocutuzumab, and it validates the potential for addressing the unmet need of patients with NRG1+ cancers,” said Andrew Joe, MD, chief medical officer, in a statement. “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.”

Zenocutuzumab is HER2/HER3 bispecific antibody that blocks NRG1 protein. A study of zenocutuzumab as treatment of patients with metastatic NRG1 gene fusion-positive solid tumors was launched after 2 patients treated with the agent through FDA-approved single-patient Investigational New Drug applications and achieved tumor shrinkage and durable tumor response. The global, open-label, multicenter phase 2 basket trial of zenocutuzumab (NCT02912949) is in progress with investigator-assessed objective response rate as its primary end point. The secondary end points are duration of response and progression-free survival.

Patients in the study are divided into 3 cohorts which include those with NRG1 fusion-positive non–small cell lung cancer (cohort 1), NRG1 fusion-positive pancreatic cancer (cohort 2), or the cohort of other NRG1 fusion-positive metastatic solid tumors (cohort 3). Cohorts 1 and 2 include 25 patients and cohort 3 can enroll a maximum of 40 patients.

Zenocutuzumab treatment in the study is administered at a dose level of 750 mg given by 2-hour infusion every 2 weeks in 4-week cycles. Patients are eligible to enroll and receive this treatment if they had at least one measurable lesion per RECIST v1.1, an ECOG performance status of 0 or 1, an estimated life expectancy of at least 12 weeks, along with adequate laboratory values at baseline and other relevant factors.

Patients in North America, Europe, and Asia are currently being accrued to the study.

_References:

_{Merus Granted FDA Fast Track designation of zenocutuzumab for the treatment of patients with neuregulin 1 fusion cancers. News release. Merus N.V. January 7, 2020. Accessed January 8, 2020. https://bit.ly/3ovIa8i}

_{Schram AM, Drilon AE, Macarulla T, et al. A phase II basket study of MCLA-128, a bispecific antibody targeting the HER3 pathway, in NRG1 fusion-positive advanced solid tumors. J Clin Oncol. 2020; 38 (suppl 15): TPS3654-TPS3654. doi: 10.1200/JCO.2020.38.15_suppl.TPS3654}