Omburtamab BLA Submitted for FDA Approval in CNS/Leptomeningeal Metastasis From Neuroblastoma

August 6, 2020

A completed Biologics License Application was submitted to the FDA for omburtamab, an investigation monoclonal antibody, which is intended for the treatment of pediatric patients with central nervous system/leptomeningeal metastasis from neuroblastoma.

A completed Biologics License Application was submitted to the FDA for omburtamab, an investigation monoclonal antibody, which is intended for the treatment of pediatric patients with central nervous system (CNS)/leptomeningeal metastasis from neuroblastoma, Y-mAbs Therapeutics, Inc announced in a press release.1

The submission is supported by data from the pivotal phase 2 101 (NCT03275402) and 03-133 (NCT00089245) clinical trials, from which results are expected to be presented later in 2020.

“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 appropriate patients. 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,” said Claus Moller, PhD, chief executive officer, Y-mAbs, Inc, in a statement.

The BLA submission follows a Breakthrough Therapy designation granted to the drug by the FDA as treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma, which was supported by findings by the single-institution study 03-133.2

In 177 patients with CNS/leptomeningeal metastasis from neuroblastoma, the median overall survival (OS) achieved with omburtamab was 50.8 months. The final median OS was not reached in the study. In comparison to interim data from the study, showing a median OS of 47.1 months in 93 patients, the data overall were promising.3

Overall, treatment with omburtamab appeared safe. Grade 3 adverse events of meningitis and increasing communicating hydrocephalus were observed in patients who received 3 injections of the drug, which led to treatment discontinuation.

Patients in the 03-133 study received a 2 mCi injection of omburtamab during week 2 of a 5-week cycle. The primary end point explored was the number of patients with treatment-related toxicities.

To be enrolled, patients were required to have a histologically confirmed diagnosis of an 8H9 reactive cancer, CNS/ leptomeningeal metastasis that is refractory to conventional treatment methods, rapidly progressing neurologic examinations, active malignancy outside the CNS, and adequate laboratory values. Although the BLA was submitted for pediatric patients, adult patients were eligible for the single-institution study.

The study excluded patients with obstructive or symptomatic communicating hydrocephalus, uncontrolled infections, pregnancy, severe toxicity in a major organ, as well as patients who received prior cranial or spin irradiation, or systemic chemotherapy.

Omburtamab was developed by researchers at Memorial Sloan Kettering Cancer Center and Y-mAbs, Inc, through a licensing arrangement. The drug is designed to target B7-H3-expressing cells in human solid tumors. Omburtamab has the potential to bind to an FG-loop-dependent conformation on the B7-H3 molecule to interfere with its biological function. In addition to brain tumors, the drug can treat embryonal tumors, carcinoma, and sarcomas.

Further clinical study of omburtamab is underway in the phase 2/3 1311 trial in combination with radioimmunotherapy in pediatric patients with neuroblastoma that has metastasized to the brain, spinal cord, or lining around the brain. The goal of the study is to evaluate the safety and efficacy of the combination.4

<<View more FDA news regarding omburtamab FDA as treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma

References:

Y-mAbs announces completion of submission of omburtamab Biologics License Application to FDA. News release. Y-mAbs, Inc. August 6, 2020, Accessed August 6, 2020. https://bit.ly/30yVGhP

Y-mAbs announces initiation of submission of omburtamab rolling Biologics License Application to the FDA. News Release. June 30, 2020. Accessed August 6, 2020. https://bit.ly/2YLCH2q

Y-mAbs announces positive pre-bla meeting with FDA for omburtamab. News release. Y-mAbs, Inc. February 26, 2020. Accessed August 6, 2020. https://bit.ly/3kgA8hI

A phase II/III study of 131i-omburtamab radioimmunotherapy in children with neuroblastoma that has spread to the brain or spinal cord or the lining around the brain. Memorial sloan Kettering Cancer Cancer website. Accessed August 6, 2020. https://bit.ly/3gDpak0