Iopofosine I-131 Demonstrates Safety and Early Efficacy in Pediatric R/R High-Grade Glioma

High-Grade Glioma |
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Iopofosine I-131 demonstrated clinical activity and was safe in pediatric patients with relapsed/refractory high-grade glioma, according to initial data from the phase 1 CLOVER-2 trial (NCT05610891).1

Data showed iopofosine I-131 had a favorable safety profile, with toxicities observed consistent with previously reported results for the agent.

Findings showed that among 7 patients who received a cumulative dose of at least 55 mCi of iopofosine I-131, the average progression-free survival (PFS) was 5.4 months, and the average overall survival (OS) was 8.6 months. All patients in this cohort achieved disease control based on Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria, which has been correlated with survival benefit in this setting.

In a subgroup of 3 patients who received a minimum 4 total infusions, the average PFS was 8.1 months, and the average OS was 11.5 months (range, 4.9-14.9); two of these patients achieved objective responses.

Iopofosine I-131 has previously received rare pediatric disease and orphan drug designations from the FDA for the treatment of pediatric high-grade glioma.

"We are highly encouraged with these initial findings from the CLOVER-2 trial in pediatric patients with high-grade glioma. Iopofosine I 131 extended PFS and survival [vs historical data], indicating potential signs of clinical efficacy for the treatment of these deadly cancers,” Jarrod Longcor, chief executive officer of Cellectar Biosciences, stated in a news release.

CLOVER-2 Trial Design

The ongoing phase 1b CLOVER-2 trial is evaluating the safety, tolerability, and preliminary efficacy of iopofosine I-131 in pediatric, adolescent, and young adult patients with relapsed or refractory high-grade glioma.2

Eligible participants include individuals with histologically confirmed relapsed or refractory high-grade glioma who were at least 10 years of age and no older than 25 years of age. Patients needed to have at least 1 intracranial lesion with a longest diameter of at least 10 mm; a Karnofsky performance status of at least 60 for patients at least 16 years of age and a Lansky performance status of at least 60 in those under 16 years of age; and adequate platelet, neutrophil, and hemoglobin levels.

The study includes 2 dosing cohorts designed to explore different schedules and total administered activity of iopofosine I-131, which is a radiotherapeutic agent that delivers targeted beta-emitting radiation to tumor cells via phospholipid ether analog uptake.1 Patients in the first cohort are receiving 2 doses at 20 mCi/m² administered 14 days apart per cycle, for up to two treatment cycles with an optional third cycle. The second cohort is being administered the agent at 10 mCi/m² on the same schedule, administered over 3 cycles with an optional fourth cycle. Dose selection was informed by preclinical data and prior adult experience with iopofosine I-131.

Safety and PFS are the trial’s primary end points.2 Overall response rate, determining the recommended phase 2/3 dose, and dosimetry are secondary end points.

Further Safety Analysis

Importantly, no cardiovascular, renal, or hepatic toxicities were reported among patients treated thus far, and there were no instances of peripheral neuropathy or clinically significant bleeding.1 The most commonly observed treatment-emergent adverse effects were hematologic and included thrombocytopenia, neutropenia, and anemia.

According to investigators, these cytopenias were anticipated and manageable. Cytopenias resolved in all patients.

References

1. Cellectar Biosciences provides update on CLOVER-2 phase 1 clinical trial of iopofosine I 131 in pediatric patients with relapsed/refractory high-grade glioma. News Release. June 11, 2025. Accessed June 11, 2025. https://www.cellectar.com/news-media/press-releases/detail/361/cellectar-biosciences-provides-update-on-clover-2-phase-1
2. Novel targeted radiotherapy in pediatric patients with inoperable relapsed or refractory HGG. ClinicalTrials.gov. Updated March 28, 2025. Accessed June 11, 2025. https://clinicaltrials.gov/study/NCT05610891