The Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee voted 16 “no” 0 “yes” on the question of whether sufficient evidence was provided to conclude that omburtamab improves overall survival in patients with CNS/leptomeningeal metastasis from neuroblastoma.

Omburtamab is an investigational radiolabeled monoclonal antibody designed to target tumor cells that express B7-H3. The BLA submission included data from 2 clinical studies, Study 101 (ClinicalTrials.gov Identifier: NCT03275402) and Study 03-133 (ClinicalTrials.gov Identifier NCT00089245), which evaluated the efficacy and safety of omburtamab in patients with CNS/leptomeningeal metastasis (LM). 

Results from Study 03-133 showed that at 3 years, the overall survival rate (primary endpoint) was 54% (95% CI, 0.43-0.64) in an efficacy population of 94 pediatric patients. These findings were compared with external control data from the Central German Childhood Cancer Registry (CGCCR), which included patients who received at least 1 type of post-CNS relapse treatment. In the external control population, the 3-year overall survival rate from the time of CNS relapse was reported to be 15% (95% CI, 0.8-0.24)

The application also included data from Study 101, in which the primary endpoint was 3-year overall survival rate; a key secondary endpoint was overall response rate. Among the 32 enrolled patients, interim results showed a 12-month overall survival of 73.5% with a median follow-up of 25 months. 

After reviewing the available evidence, the panel identified 3 key efficacy issues. These included the external control population not being a relevant comparator, an inability to attribute the differences in survival to omburtamab after performing multiple sensitivity analyses, and a lack of reliable response rate data to support a treatment effect.

“In summary, the identified substantive review issues call into serious question whether the CGCCR-derived patient population is an appropriate comparator. In addition, there is no reliable information on tumor response rate, leading to significant questions as to whether the submitted study can be considered an adequate and well-controlled trial necessary to establish effectiveness,” the FDA panel explained in the briefing document. “Without substantial evidence of effectiveness, FDA cannot determine whether the risk:benefit relationship for use of omburtamab in patients with CNS/LM relapsed neuroblastoma is favorable.”

The Biologics License Application for omburtamab was accepted for Priority Review in May 2022. A decision on the application is expected on November 30, 2022. Although not bound by the committee’s recommendations, the FDA does take them into consideration when making decisions on approval.

References

  1. Y-mAbs announces outcome of FDA advisory committee meeting on omburtamab. New York, NY. News release. October 28, 2022. https://www.globenewswire.com/news-release/2022/10/28/2544126/0/en/Y-mAbs-Announces-Outcome-of-FDA-Advisory-Committee-Meeting-on-Omburtamab.html
  2. US Food and Drug Administration. FDA Briefing Document: 131I-omburtamab. Accessed November 1, 2022.
  3. https://www.fda.gov/media/162614/download
  4. Y-mAbs announces pivotal data for omburtamab. New York, NY. News release. October 3, 2022. https://ir.ymabs.com/news-releases/news-release-details/y-mabs-announces-pivotal-data-omburtamab