FDA Grants Fast Track Designation to Seribantumab for NRG1+ Advanced Solid Tumors

The FDA has granted fast track designation to seribantumab for the treatment of advanced solid tumors that harbor NRG1 gene fusions, announced Elevation Oncology, Inc, in a press release.¹

Seribantumab is a fully human IgG2 monoclonal antibody that binds to HER3 by way of the NRG1 ligand. NRG1 gene fusions are rare and unique oncogenic driver that have been shown to be associated with tumor cell survival. NRG1 fusions have been identified in patients with solid tumors including ling cancer. Pancreatic cancer, gallbladder cancer, breast cancer, colorectal cancer, neuroendocrine tumor, cholangiocarcinoma, and sarcomas.

"There are currently no approved therapies that specifically target NRG1 fusions, and therefore, receipt of Fast Track designation in a tumor-agnostic setting is a significant step in addressing this unmet need," said Shawn M. Leland, PharmD, RPh, founder and chief executive officer of Elevation Oncology, in a press release. "NRG1 fusions are a type of genomic alteration that causes unregulated cell growth and proliferation in a variety of solid tumors, and we look forward to working closely with the FDA as we continue exploring the potential of seribantumab to improve outcomes for patients whose tumor harbors this unique oncogenic driver."

Seribantumab treatment is being assessed in the open-label, multicenter, phase 2 CRESTONE clinical trial. In the study 75 patients with locally advanced or metastatic solid tumors that harbor a NRG1 gene fusion will be divided into 3 cohorts. Cohort 1 of the study will include 55 adult patients with advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, with the exception of prior ERBB-directed therapy. In cohort 2, up to 10 adult patients with advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, including prior ERBB-directed therapy will be enrolled. In cohort 3, up to 10 adult patients who have advanced solid tumor patients harboring NRG1 gene fusions lacking an EGF-like domain, who have received prior standard treatment, which may have included prior ERBB-directed therapy will be included.²

In all cohorts, seribantumab will be administered via 1-h intravenous infusion at various dose levels once weekly. In terms of the dose schedule, treatment with the investigational agent will be given every 2 weeks and every 3 weeks during the induction, consolidation, and maintenance phase.

The primary end point being investigated in objective response rate which is determined by independent radiologic and according to RECIST v.1.1.

To be eligible for inclusion, patients with locally-advanced or metastatic solid tumor with an NRG1 gene fusion identified through molecular, assays must have available tissue for biopsies, have received a minimum of 1 prior standard therapy, be at least 18 years of age or older, have an ECOG performance status of 0,1, or 2, as well as adequate hepatic function, laboratory tests, hematologic status.

The study excludes patients who have a known actionable driver mutation other than a NRG1 fusion. In addition, patients with a life expectancy of < 3 months, are pregnant or lactating, have received prior treatment with ERBB2/HER3 directed therapy, have symptomatic or untreated brain metastases, any other active malignancy requiring systemic therapy, clinically significant cardiac disease, active uncontrolled systemic bacterial, viral, or and fungal infection. In terms of prior therapy, patients who received another investigation agent or anticancer therapy within 28 days of seribantumab, had prior initiation of seribantumab treatment, or are not appropriate candidates for participation in the clinical trial at the investigator’s discretion.

With a fast track designation, seribantumab may have expedited drug development by the FDA. The drug will also be eligible for priority review and accelerated approval is relevant criteria are met.¹

_REFERENCES:

_{1. Elevation Oncology announces FDA fast track designation granted to seribantumab for the tumor-agnostic treatment of solid tumors harboring NRG1 gene fusions. New release. Elevation Oncology. May 25, 2022. Accessed May 25, 2022. https://bit.ly/3Nv1Dlo}

_{2. Study of seribantumab in adult patients with NRG1 gene fusion positive advanced solid tumors. Clinicaltrials.gov. Updated April 19. 2022. Accessed May 25, 2022.}