In an interim readout from the Phase 1b CLOVER-2 study in relapsed/refractory pediatric high-grade glioma (pHGG), patients receiving at least 55 mCi total iopofosine I 131 achieved a mean progression-free survival of 5.4 months and overall survival of 8.6 months (ongoing), with disease control in all evaluable patients. A subset receiving four or more infusions posted a mean PFS of 8.1 months and OS of 11.5 months (range 4.9–14.9 months), including two objective responses. These signals compare against historical expectations in relapsed pHGG of approximately 2.25 months PFS and 5.6 months OS. Safety was dominated by predictable hematologic events; no clinically meaningful cardiac, renal, hepatic, peripheral neuropathy, or major bleeding toxicities were observed.
The company presented the data at AACR’s Special Conference on Pediatric Cancer, framing them as dose and regimen optimization findings for a potential first-in-class phospholipid ether radioconjugate monotherapy. CLOVER-2 is an active-but-not-enrolling, multi-site U.S./Canada Phase 1b trial in children, adolescents, and young adults with inoperable r/r pHGG, evaluating two dosing schemas and intended to identify a recommended Phase 2/3 dose while characterizing therapeutic activity by RAPNO criteria. Iopofosine I-131 holds Orphan and Rare Pediatric Drug designations in pHGG, positioning the asset for a potentially expedited pediatric pathway and a PRV upon approval.
Strategically, Cellectar is testing whether a targeted radiotherapeutic with manageable marrow toxicity can carve out a monotherapy niche in a setting where effective systemic options are scarce and re-irradiation often defines the control arm. The exposure–response hint is notable: outcomes appeared stronger at higher cumulative activity and with additional cycles. That matters operationally because the development path may hinge on repeat dosing feasibility without prohibitive cytopenias. It also puts Cellectar inside the current radiopharmaceutical tailwind while sidestepping the manufacturing and supply constraints of actinium-based agents by leveraging iodine-131 and a small-molecule delivery platform.
The tension is evident. CLOVER-2 spans a biologically heterogeneous population (DMG/DIPG, DHG, ependymoma), the sample is small, and the study is uncontrolled. While disease control per RAPNO correlates with survival, regulators have tightened expectations around single-arm pediatric neuro-oncology filings. An accelerated path based on objective response and duration looks challenging given the limited number of confirmed responses to date; a survival-based strategy confined to a clearer subgroup (e.g., DMG/DIPG) may be more credible but will demand meticulous historical control construction or randomization against re-irradiation/best supportive care.
For sites, the signal invites participation but underscores capacity constraints. Pediatric radiopharmaceutical delivery requires nuclear medicine infrastructure, radiation safety protocols, dosimetry, and support for repeat cycles with hematologic monitoring. Enrollment will likely cluster at large pediatric neuro-oncology centers with established radiation handling, which could slow accrual unless the network expands. CROs and vendors will need tight logistics for isotope supply and timing, centralized imaging with RAPNO-consistent volumetrics, and standardized algorithms for dose holds and growth-factor use.
Next, watch for a final Phase 1b data cut, the recommended Phase 2/3 dose, and a clarified registrational strategy—single-arm in a defined histology versus randomized. Durability beyond 12 months, consistency across subtypes, and marrow tolerance over multiple cycles will be decisive. Operational risks include isotope availability and site throughput in pediatric settings; regulatory risk centers on the sufficiency of survival evidence without randomization. If the exposure–response observation holds in a larger, more homogeneous cohort and logistical execution improves, the program could advance, but the bar for a pediatric glioma approval remains high, and timelines will hinge on site activation depth and sustained manufacturing reliability.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
