There is insufficient evidence that the pediatric oncology drug 131-I-omburtamab enhances overall survival, the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted unanimously on Oct. 28.
131-I-omburtamab is an iodine-131 radiolabeled antibody that targets B7-H3 on neuroblastoma cells. The treatment was developed to treat central nervous system/leptomeningeal (CNS/LM) metastases in pediatric patients with neuroblastoma, after standard multimodality treatment for CNS disease. It is given through intraventricular administration.
The treatment was tested via a single-center, single-arm phase 1 study at Memorial Sloan Kettering Cancer Center in New York City. The FDA also received interim data from an ongoing international, multi-center, single-arm trial of 131-I-omburtamab, whose survival data are immature. Y-mAbs Therapeutics submitted a Biologics License Application in March 2022.
“We all want to provide more to these patients,” said Christopher Lieu, MD, associate director for clinical research at the University of Colorado Cancer Center in Aurora. But, he added, the study lacks sufficient data and “a clear response rate.”
All 16 present voting members of ODAC voted “no” in response to the question about 131-I-omburtamab. Many said that data do not isolate the drug’s treatment effect; they called for additional data from randomized controlled trials, especially.
“There’s a lot of uncertainty in these data,” said Michael Hudgens, PhD, professor and associate chair of the Department of Biostatistics at the University of North Carolina-Chapel Hill.
The MSK study enrolled 94 patients, who were treated with three different dose sizes, depending on age (spanning 0.9 to 13 years). The patients were administered up to two doses each – given five weeks apart. Patients were enrolled between 2004-2018. Every patient also received at least one type of CNS-directed therapy before getting I-omburtamab, with 76% receiving all three types of therapy – surgery, chemotherapy, and radiotherapy.
Results showed that 54% of the patients lived another three years after their first CNS/LM relapse diagnosis.
Researchers compared these results with an external German control group including patients treated for stage 4 neuroblastoma between 1990-2015. They found 79 patients who had received at least one of the three post-CNS relapse therapies.
An FDA background document accompanying the meeting noted several key differences across the patient populations. ODAC committee members cited these issues and others. “The statistical analyses were limited,” said Julie R. Park, MD, a pediatrics professor at the University of Washington School of Medicine and Seattle Children’s Hospital.
“This really looks to me like this is a lot of selection bias,” said Jorge J. Nieva, MD, associate professor of clinical medicine at University of Southern California’s Keck School of Medicine.
Other committee members lamented that exact doses administered to the external group were not reported.
Committee members commended Y-mAbs for pursuing this treatment – especially when it stands to be used by only a handful of patients in the U.S. annually, according to members and meeting background documents. They encouraged the company to continue pursuing this work.
“There’s no question this is an unmet need,” said Nita Seibel, MD, head of pediatric solid tumor therapeutics at the National Cancer Institute and National Institutes of Health.
“This is very hard to do, and this work highlights a lot of the difficulties we face,” said E. Anders Kolb, MD, who directs the Nemours Center for Cancer and Blood Disorders at Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia.
