FDA Issues Refusal to File Letter for Omburtamab for Pediatric Metastatic Neuroblastoma

The FDA has issued a Refusal to File letter regarding the biologics license application for the investigational B7-H3–targeting monoclonal antibody omburtamab for the treatment of pediatric patients with central nervous system/leptomeningeal metastasis from neuroblastoma.

The FDA has issued a Refusal to File letter regarding the biologics license application (BLA) for the investigational B7-H3–targeting monoclonal antibody omburtamab for the treatment of pediatric patients with central nervous system (CNS)/leptomeningeal metastasis from neuroblastoma, according to Y-mAbs Therapeutics Inc.1

Following preliminary review of the data submitted for the agent, the regulatory agency determined that certain portions of the Chemistry, Manufacturing, and Control (CMC) module and the Clinical module of the application require further detail. However, no non-clinical data have been requested.

The biopharmaceutical company shared plans to address the concerns raised by the FDA by providing additional CMC information, along with supplementary findings from Study 101 focused on tumor response with the agent in the first 24 patients included in the study protocol who are evaluable for disease. Furthermore, Y-mAbs announced that they will request a Type A meeting with the FDA to adequately amend the BLA before the end of this year.

The BLA for omburtamab was submitted to the FDA in August 2020 under the agency’s Rolling Review process, based on safety and efficacy findings from 2 pivotal phase 2 trials: Study 101 (NCT03275402) and Study 03-133 (NCT00089245). The data from these trials are expected to be presented later in 2020.2

Omburtamab was developed to bind to the surface of neuroblastoma cells. Once connected to the radioisotope, the monoclonal antibody becomes a favorable option for radioimmunotherapy, according to Y-mAbs. The drug is given via injection into the spinal fluid; once injected, it is designed to dispense precise liquid radiation to eliminate cancer cells.3 The agent was developed by investigators at Memorial Sloan Kettering Cancer Center and it has exclusively been licensed by the institution to the biopharmaceutical company.

In June 2017, the FDA granted a breakthrough therapy designation to omburtamab based on findings from the Study 03-133 trial, which had enrolled a total of 177 patients with CNS/leptomeningeal metastases from neuroblastoma. Participants received up to 2 doses of the agent.

Results from the trial showed that omburtamab resulted in a median overall survival (OS) of 50.8 months, although the final OS had not yet been reached at the time of presentation.4 The first 93 patients who enrolled on the study experienced a median OS of 47.1 months. Additionally, 68 patients with other CNS cancers, such as metastatic tumors, were given a sum of 201 omburtamab injections in the outpatient setting.

Omburtamab was found to be safe, and self-limited adverse effects (AEs) were rare, but included fever, headache, and vomiting; these effects were only grade 1 or 2. However, 3 injections were linked with grade 3 AEs that resulted in treatment discontinuation; these patients experienced meningitis and increasing communicating hydrocephalus. Additionally, patients who underwent craniospinal radiation at dose levels higher than 60 mCi experienced myelosuppression, although this effect was not determined to be a dose-limiting toxicity.

Omburtamab is under exploration in a phase 2 trial (NCT04022213) to see whether it is capable of preventing or delaying the worsening of desmoplastic small round cell tumors or other cancers of the peritoneum.5 The trial is currently recruiting patients for participation and the primary objective is progression-free survival.


  1. Y-mAbs provides regulatory update on omburtamab for the treatment of patients with neuroblastoma. News release. Y-mAbs Therapeutic, Inc. October 5, 2020. Accessed October 5, 2020. https://bit.ly/30Dgq7B.
  2. Y-mAbs announces completion of submission of omburtamab biologics license application to FDA. News release. Y-mAbs Therapeutics, Inc. August 6, 2020. Accessed October 5, 2020. https://bit.ly/3khYdEQ.
  3. Burtomab receives breakthrough therapy designation for advanced form of pediatric cancer. News release. Business Wire. June 7, 2017. Accessed October 5, 2020. https://bwnews.pr/2NJPf49.
  4. Y-mAbs announces positive pre-BLA meeting with FDA for omburtamab. News release. Y-mAbs Therapeutics, Inc. February 26, 2020. Accessed October 5, 2020. https://bit.ly/3dO4UKc.
  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 October 5, 2020. https://clinicaltrials.gov/ct2/show/NCT04022213.