Iopofosine I 131 Shows Preliminary Survival Benefit in Pediatric R/R Glioma

Developers designed iopofosine I 131 to leverage a proprietary phospholipid-drug conjugate platform to deliver the radioisotope iodine 131. This novel delivery platform is intended to limit off-target effects during administration, thereby improving the efficacy and safety of treatment.

Treatment with iopofosine I 131 demonstrated early survival benefit in a small cohort of pediatric patients with relapsed/refractory high-grade gliomas, according to a press release on preliminary findings from the phase 1b CLOVER-2 trial (NCT03478462) from the drug’s developer, Cellectar Biosciences, Inc.¹

Among 7 patients who received the agent at a minimum total dose of 55 mCi, the average progression-free survival (PFS) was 5.4 months and overall survival (OS) was 8.6 months. Disease control occurred in all patients, which may correlate with survival benefit per Response Assessment in Pediatric Neuro-Oncology criteria.

Of 3 patients who received additional doses of iopofosine I 131 for at least 4 infusions, the average PFS was 8.1 months and the average OS was 11.5 months (range, 4.9-14.9). Investigators noted an objective response in two of these patients.

Iopofosine I 131 appeared to be tolerable in the CLOVER-2 trial, and its safety profile was comparable with prior reports of the agent. No patients had cardiovascular, renal, or liver toxicities following treatment, and investigators observed no cases of peripheral neuropathy or significant bleeding.

Treatment with iopofosine I 131 showed clinically negligible off-target effects outside the hematologic system. The most frequent treatment-emergent adverse effects consisted of hematologic toxicities such as thrombocytopenia, neutropenia, and anemia, which were predictable and manageable. All instances of cytopenia eventually subsided.

“We are highly encouraged with these initial findings from the CLOVER-2 trial in pediatric patients with high-grade glioma. Iopofosine I 131 observed extended PFS and survival, indicating potential signs of clinical efficacy for the treatment of these deadly cancers,” Jarrod Longcor, chief operating officer of Cellectar Biosciences, stated in the press release.¹ “We believe this outcome further validates the clinical potential of iopofosine I 131 to treat aggressive cancers for patients with limited treatment options.”

Developers designed iopofosine I 131 to leverage a proprietary phospholipid-drug conjugate platform to deliver the radioisotope iodine 131. This novel delivery platform is intended to limit off-target effects during administration, thereby improving the efficacy and safety of treatment.

Investigators of the open-label, dose-escalation CLOVER-2 trial are evaluating the efficacy and safety of iopofosine I 131 among children, adolescents, and young adults with select solid tumors, lymphoma, and malignant brain tumors.² An estimated population of 30 patients will receive iopofosine I 131 intravenously as a single or fractionated dose.

The trial’s primary end point is the number of patients with dose-limiting toxicities. Secondary end points include the recommended phase 2 dose, preliminary antitumor activity, event-free survival, OS, and dosimetry.

Patients aged 2 to 25 years with previously confirmed pediatric solid tumors, lymphoma, or malignant tumors that were radiographically or clinically suspected to be relapsed, refractory, or recurrent with no curative therapy options were eligible for trial enrollment. Other requirements for study entry included having a Karnofsky performance status of 60 or higher or a Lansky performance status of 60 or higher, adequate platelet counts, and a period of at least 3 months following prior autologous or allogeneic bone marrow transplant. Those with recurrent or refractory brain tumors were required to have at least 1 measurable lesion with the longest diameter of 10 mm or longer on any imaging sequence.

Those receiving active treatment for central nervous system metastases or those who were likely to require active therapy during anticipated enrollment were ineligible for study entry. Patients who received any investigational therapy or antitumor treatment within 2 weeks of beginning treatment with iopofosine I 131 were unable to enroll in the trial.

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. Cellectar Biosciences Inc. June 11, 2025. Accessed June 11, 2025. https://tinyurl.com/y5dvh5cj
2. Dose escalation study of CLR 131 in children, adolescents, and young adults with relapsed or refractory malignant tumors including but not limited to neuroblastoma, rhabdomyosarcoma, Ewings sarcoma, and osteosarcoma (CLOVER-2). ClinicalTrials.gov. Updated March 28, 2025. Accessed June 11, 2025. https://tinyurl.com/4rw43rvj