FDA Approval Sought for Omburtamab in Pediatric Metastatic Neuroblastoma

The biologics license application for the investigational B7-H3–targeting monoclonal antibody omburtamab for use in pediatric patients with central nervous system/leptomeningeal metastases from neuroblastoma has been submitted to the FDA under the agency’s Rolling Review process.

The biologics license application (BLA) for the investigational B7-H3–targeting monoclonal antibody omburtamab for use in pediatric patients with central nervous system (CNS)/leptomeningeal metastases from neuroblastoma has been submitted to the FDA under the agency’s Rolling Review process, according to Y-mAbs Therapeutics, Inc.1

The submission is based on the safety and efficacy data from 2 pivotal phase 2 trials: 101 (NCT03275402) and 03-133 (NCT00089245). Findings from the trials are anticipated to be presented later in 2020, according to the late-stage clinical biopharmaceutical company.

“I am excited to see the completion of Y-mAbs’ second BLA submission this year in neuroblastoma. As children treated for high-risk systemic neuroblastoma potentially experience longer systemic remissions, we expect more patients eventually relapsing with brain metastases and there is currently no standard therapy available for these patients,” Thomas Gad, founder, chairman, and president of Y-mAbs, stated in a press release. “We believe this is a key milestone for families facing CNS/leptomeningeal metastasis from neuroblastoma and for Y-mAbs.”

The monoclonal antibody was designed to bind to the surface of neuroblastoma cells. When connected to the radioisotope, it becomes a favorable agent for radioimmunotherapy. The agent is delivered via injection into the spinal fluid; there, omburtamab delivers precise liquid radiation to kill cancer cells.2 The drug was developed by investigators from Memorial Sloan Kettering (MSK) Cancer Center; it is exclusively licensed by MSK to Y-mAbs.

Previously, in June 2017, the FDA granted a breakthrough therapy designation to omburtamab based on findings from the single-center Study 03-133 trial. A total of 177 patients with CNS/leptomeningeal metastases from neuroblastoma were included, and they received up to 2 doses of the radiolabeled drug.

Data demonstrated a median overall survival (OS) of 50.8 months with omburtamab; however, the final median OS had not yet been reached.3 These data favorably compared with the 47.1-month median OS reported in the first 93 patients who had been enrolled on the study. Additionally, 68 patients with other CNS cancers, such as metastatic tumors, received a sum of 201 omburtamab injections, in the outpatient setting.

The monoclonal antibody was found to be safe, successfully targeting cancer cells while avoiding surrounding brain tissues. Self-limited adverse effects (AEs) were rare, but included fever, headache, and vomiting; all these toxicities were grade 1/2 in severity.

Three injections were associated with grade 3 AEs which led to treatment discontinuation; these toxicities included meningitis and increasing communicating hydrocephalus. Notably, patients who received craniospinal radiation at dose levels over 60 mCi reported myelosuppression; however, this had not been considered to be a dose-limiting toxicity.

The primary CNS diagnoses included medulloblastoma (n = 27), ependymoma (n = 9), and embryonal tumors with multilayered rosettes (n= 4). Metastatic tumors included sarcoma (n = 9), melanoma (n = 5), and others (n = 14). Twenty-six of 68 patients with these potentially deadly diagnoses remained alive, as of October 28, 2019.4

“We believe omburtamab can potentially address a significant unmet need for children with CNS/leptomeningeal metastasis from neuroblastoma, and we look forward to working with the FDA to bring omburtamab to appropriate patients,” Claus Moller, MD, PhD, chief executive officer at Y-mAbs, stated in the release. “Omburtamab is also being tested in a phase 2 study for desmoplastic small round cell tumor and we are currently planning a phase 2 study for diffuse intrinsic pontine glioma, as we believe omburtamab could potentially be developed for wider compartmental use.”

In a phase 2 trial (NCT04022213), investigators hope to determine whether treatment with omburtamab can prevent or delay the worsening of desmoplastic small round cell tumors or other cancers of the peritoneum.5 The primary end point of the trial, which is now in the process of recruiting patients, is progression-free survival.


  1. Y-mAbs announces completion of submission of omburtamab biologics license application to FDA. News release. Y-mAbs Therapeutics, Inc. August 6, 2020. Accessed August 6, 2020. https://bit.ly/3khYdEQ.
  2. Burtomab receives breakthrough therapy designation for advanced form of pediatric cancer. News release. Business Wire. June 7, 2017. Accessed June 30, 2020. bwnews.pr/2NJPf49.
  3. Y-mAbs announces positive pre-BLA meeting with FDA for omburtamab. News release. Y-mAbs Therapeutics, Inc. February 26, 2020. Accessed June 30, 2020. bit.ly/3dO4UKc.
  4. Y-mAbs announces positive omburtamab clinical data. News release. October 28, 2019. Accessed June 30, 2020. bit.ly/2YKpw1W.
  5. A study of the drug I131-omburtamab in people with desmoplastic small round cell tumors and other solid tumors in the peritoneum. ClinicalTrials.gov. Updated May 12, 2019. Accessed August 6, 2020. https://clinicaltrials.gov/ct2/show/NCT04022213.