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A biologics license application seeking the approval of 131I-omburtamab in the treatment of pediatric patients with central nervous system/leptomeningeal metastases from neuroblastoma has been resubmitted to the FDA.
A biologics license application (BLA) seeking the approval of 131I-omburtamab in the treatment of pediatric patients with central nervous system (CNS)/leptomeningeal metastases from neuroblastoma has been resubmitted to the FDA, according to an announcement from Y-mAbs Therapeutics, Inc.1
Omburtamab is a radiolabeled monoclonal antibody 8H9(131I-8H9) that was designed to target B7-H3–expressing cells in solid tumors, including embryonal tumors, carcinomas, sarcomas, and brain tumors.2 The agent, which was developed by researchers at Memorial Sloan Kettering Cancer Center, has been shown to bind to an FG loop-dependent conformation on the B7-H3 molecule, which plays a key role in biologic function.
The BLA is supported by safety and efficacy findings from 2 pivotal phase 2 trial: 101 (NCT03275402) and 03-133 (NCT00089245), which are expected to publish later this year.
“I am excited to see the completion of Y-mAbs’ second BLA submission in neuroblastoma. As children treated for high-risk systemic neuroblastoma potentially experience longer systemic remissions, we expect more patients eventually relapsing with brain metastasis and there is currently no effective therapy beyond surgery and radiotherapy available for these patients,” Thomas Gad, founder, chairman, and president of Y-mAbs Therapeutics, Inc., stated in a press release.
The BLA for omburtamab was originally submitted to the regulatory agency in August 2020 under the Rolling Review process.3 However, in October 2020, following a preliminary review of data submitted for the agent, the FDA determined that certain points of the Chemistry, Manufacturing, and Control (CMC) module and the Clinical module of the application required additional detail. Although no non-clinical data were requested, the FDA issued a Refusal to File letter.4
The biopharmaceutical company shared that they planned to address the concerns raised by the agency by providing more CMC information and including supplementary data from Study 101 on tumor response in the first 24 evaluable patients.
The company announced plans to resubmit the BLA in April 2021, after a Type B meeting was held with the FDA.5 At that time, the agency requested additional information surrounding the granularity of data from identified historical control groups used in the first application for the agent in this indication. An additional Type B meeting was scheduled for June 2021 to discuss a statistical analysis plan after they reviewed the additional findings.
Previously, in July 2017, the FDA granted a breakthrough therapy designation to omburtamab based on data yielded from Study 03-133, which had enrolled a total of 177 patients with CNS/leptomeningeal metastases from neuroblastoma. Participants had received up to 2 doses of the agent.6
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 the presentation.7 Among the first 93 patients who had been enrolled to the trial, the median OS with omburtamab was 47.1 months.
Although self-limited adverse effects with the agent proved to be rare, they included fever, headache, and vomiting; all these effects were grade 1 or 2 in severity. Three injections were associated with grade 3 toxicities that led to treatment discontinuation. Specifically, these patients had meningitis and increasing communicating hydrocephalus.
Patients who received craniospinal radiation at a dose that was higher than 60 mCi experienced myelosuppression, but this adverse effect was not considered to be a dose-limiting toxicity.
“We believe omburtamab can potentially address a significant unmet medical need for children with CNS/leptomeningeal metastasis from neuroblastoma, and we look forward to working with the FDA to bring omburtamab to the appropriate patients,” Claus Moller, MD, PhD, stated in a press release. “This is a key milestone for families and patients facing CNS/leptomeningeal metastasis from neuroblastoma and for Y-mAbs.”