As part of a resubmission plan for a biologics license application for omburtamab in pediatric patients with central nervous system and leptomeningeal metastasis from neuroblastoma, Y-mAbs, the manufacturer of the B7-H3–targeting monoclonal antibody, announced that it is collecting additional granularity data requested by the FDA and anticipates submitting them to the regulatory agency by the end of April 2021.
As part of a resubmission plan for a biologics license application (BLA) for omburtamab in pediatric patients with central nervous system (CNS) and leptomeningeal metastasis from neuroblastoma, Y-mAbs, the manufacturer of the B7-H3–targeting monoclonal antibody, announced that it is collecting additional granularity data requested by the FDA and anticipates submitting them to the regulatory agency by the end of April 2021.1
The announcement follows a Type B meeting with the FDA regarding omburtamab, in which the agency requested additional findings surrounding the granularity of data from identified historical control groups used in the first BLA for omburtamab in this indication. The results are essential to an agreement on a statistical analysis plan for resubmission.
Y-mABs stated that an additional Type B meeting with the FDA has been scheduled for June 1, 2021, to discuss the statistical analysis plan following review of the additional data. The company noted that it anticipates resubmitting the BLA for omburtamab in the second or third quarter of 2021.
"We believe omburtamab is on track to potentially become the first FDA-approved targeted therapy for pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma, addressing an important unmet medical need, where no standard therapy is currently available," said Thomas Gad, founder, Chairman and president of Y-mAbs.
The news follows the October 2020 announcement that the FDA issued a Refusal to File letter regarding the BLA for omburtamab in pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma.2
Following preliminary review of the data submitted for omburtamab, the FDA 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 had been requested.
Y-mAbs previously noted that it planned to address the agency’s concerns 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.
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 2020.3
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. It is given as an injection into the spinal fluid and then dispenses precise liquid radiation to eliminate cancer cells.4 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.
The FDA granted a breakthrough therapy designation to omburtamab in July 2017 based on results from Study 03-133, which enrolled 177 patients with CNS/leptomeningeal metastases from neuroblastoma. Patients received up to 2 doses of treatment.
Results showed that omburtamab led to a median overall survival (OS) of 50.8 months; the final OS had not yet been reached at the time of presentation.5 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.
Regarding safety, 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.6 The trial is currently recruiting patients for participation and the primary objective is progression-free survival.
“We believe omburtamab can potentially address a significant unmet medical need for children with CNS/leptomeningeal metastasis from neuroblastoma, and we continue to work closely with the FDA to resubmit the omburtamab BLA,” Claus Moller, MD, chief executive officer of Y-mAbs, stated. “In addition, we are targeting submission of a Marketing Authorization Application to the European Medicines Agency on April 30, 2021.”