FDA Grants Rare Pediatric Designation for Iopofosine-131 in Glioma Subset

The U.S. Food and Drug Administration (FDA) has granted rare pediatric drug designation for iopofosine-131 in inoperable relapsed or refractory pediatric high-grade glioma (pHGG), according to a news release from Cellectar Biosciences.

The FDA’s rare pediatric disease designation program supports the development of treatments for serious conditions that mainly affect children under 18.

“Receiving rare pediatric disease designation for iopofosine-131 underscores its potential to address one of the most devastating cancers affecting children and young adults. Combined with the encouraging interim results from our CLOVER-2 pHGG study, which showed meaningful improvements in progression-free and overall survival, this designation further validates the promise of our targeted radiotherapeutic approach,” James Caruso, president and CEO of Cellectar, stated in the news release. “We believe iopofosine-131 represents a compelling opportunity for strategic collaboration to accelerate development and bring a potentially first-in-class therapy to patients who urgently need new options.”

Interim findings from the CLOVER-2 study were recently shared at the American Association for Cancer Research Special Conference on Pediatric Cancer, held in September 2025. The phase 1b trial is evaluating iopofosine-131, a targeted radiotherapy, in children, adolescents and young adults in the United States and Canada with relapsed or refractory pediatric high-grade glioma, a rare and aggressive brain cancer.

In an oral presentation during the conference, the company’s chief operating officer, Jarrod Longcor, reported encouraging early results.

Among patients who received at least 55 millicuries (mCi) of the total administered dose (6 patients), the average progression-free survival (PFS) was 5.4 months and the average overall survival (OS) was 8.6 months, with both ongoing at the time of the report. All patients experienced disease control, which the Response Assessment in Pediatric Neuro-Oncology committee notes can correlate with improved survival.

Three patients who received at least four infusions showed an average PFS of 8.1 months and an zos of 11.5 months, ongoing, with two experiencing measurable tumor shrinkage.

Individual Outcomes Reported With Iopofosine-131 in Pediatric Brain Cancers

Two case studies presented as part of the CLOVER-2 trial update highlighted encouraging outcomes in young patients with rare and aggressive brain tumors treated with iopofosine-131.

Case Study 1: A 25-year-old man with diffuse hemispheric glioma carrying the H3 G34R/V mutation, who had undergone three previous treatments, received four doses of iopofosine-131 totaling 126.6 mCi (40 mCi/m² per dose). Approximately eight months after screening, his target lesion had decreased by more than 50%. His progression-free survival was 10.9 months, and as of July 25, 2025, he remained alive more than 18 months after starting treatment.

Case Study 2: A 15-year-old girl with ependymoma, who had received eight prior therapies, was treated with four doses totaling 58.9 mCi of iopofosine I 131 (20 mCi/m² per dose). Her tumor size decreased from 252 mm² to about 141 mm². Her progression-free survival was 11.2 months, and as of July 22, 2025, she remained alive more than 17 months after treatment initiation.

How Safe Is Iopofosine-131 for Children and Young Adults With Brain Cancer?

Iopofosine-131 was generally well tolerated in the CLOVER-2 trial, with side effects consistent with previously reported safety findings. Notably, no patients experienced heart, kidney or liver toxicity, and there were no cases of peripheral neuropathy or significant bleeding.

The treatment’s safety profile reflected its targeted design, with minimal effects outside the blood system. The most common side effects were hematologic, including low platelet counts (thrombocytopenia), low white blood cell counts (neutropenia) and anemia, all of which were expected and manageable. No treatment-related deaths were reported.

How Does the CLOVER-2 Study Test Iopofosine-131 in Pediatric Brain Cancer?

The phase 1b CLOVER-2 study is enrolling children, adolescents and young adults in the United States and Canada who have relapsed or refractory pediatric high-grade glioma. Its goal is to assess how safe and tolerable iopofosine-131 is at different dosing schedules.

One group receives two doses of 20 mCi/m², given 14 days apart for two cycles, with an optional third cycle. The other group receives three cycles of 10 mCi/m², also given 14 days apart, with an optional fourth cycle.

Researchers will evaluate how well the treatment controls tumor growth by measuring PFS and OS, as well as tumor volume reduction, to help determine the optimal dose for later-phase studies.

Reference

1. “Cellectar Biosciences Receives Rare Pediatric Disease Designation from U.S. Food and Drug Administration for Iopofosine I 131 in Relapsed or Refractory Pediatric High-Grade Glioma.” Cellectar Biosciences. News Release. Oct. 27, 2025.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.