Abstract A019: Precision radiotherapy for incurable brain tumors: Phase 1b dose & regimen optimization study of iopofosine I 131 in inoperable relapsed or refractory pediatric high-grade glioma, interim data assessment

Abstract Iopofosine I 131, a radioconjugate therapy targeting tumor lipid rafts, is being assessed in CLOVER-2–an ongoing dose-finding study in children, adolescents, and young adults with malignant brain tumors. Part A [NCT03478462] was a dose escalation phase enrolling patients (pts) aged 2-25 years (yrs) with measurable solid tumors, lymphomas or malignant brain tumors. Pts received either a single dose (15-30 mCi/m2) on Day 1 or fractionated dose (total dose 45-75 mCi/m2) on Days 1 and 15 in a 12-week Cycle; an additional cycle was allowed at investigator discretion. Part B [NCT05610891] is an expansion in pts with high grade glioma (HGG) or ependymoma to evaluate 2 dosing regimens. Arm 1pts receive 2 doses of 20 mCi/m2 given 14 days apart (± 1 day) for 2 cycles. Arm 2 pts receive 2 doses of 10 mCi/m2 14 days apart for 3 cycles. Pts in either Arm are eligible for 1 additional cycle at the investigator's discretion. Major entry criteria include pts aged 10-25 yrs, ≥1 measurable intracranial lesion (≥10mm), and PS ≥60. A total of 14 pts with brain malignancies have been enrolled, including 6 with ependymoma, 4 with diffuse intrinsic pontine glioma, and 1 each with diffuse hemispheric glioma (DHG), diffuse midline glioma, medulloblastoma, and glioblastoma multiforme. The median age is 13 yrs (range 5-25 yrs) and includes 9 males and 5 females with a mean of 4.4 prior interventions. Seven pts received at least 55 mCi total administered dose (TAD) of whom 6 are efficacy-evaluable; 7 received < 55 mCi of whom 5 are evaluable; 3 received only a single cycle and were considered unevaluable. There were 2 minor responses reported; both in pts who received ≥ 55 mCi. One pt with DHG experienced an initial 35% reduction in target lesions and a continued reduction to 50%at 8 months post-treatment but a new lesion was noted at the same time. A second pt with ependymoma experienced a 31% reduction in the target lesion. All pts who received at least 55 mCi TAD reported stable disease resulting in a 100% disease control rate with an average duration of 5.4 months (range 1.9-11.0 months). The mean progression free survival (PFS) in pts who received ≥ 55 mCi (n=6) was 5.9 months (range 2.1-11.2) and mean overall survival (OS) of 8.1 months (range 4.9 to 14.9 months). Importantly Part B pts (n=3) achieving a minimum of 55 mCi and receiving multiple cycles demonstrated PFS of 8.1 months with OS ongoing (median follow up 11.5 months, range 4.9-14.9 months). In comparison, for pts who received < 55 mCi (n=5) the mean PFS was 1.8 months (range 1.2-2.8). The safety profile was consistent with selective targeting of tumor sites with clinically negligible off-target effect outside the hematologic system. The most common treatment emergent adverse events (AE) are: thrombocytopenia (79%), anemia (64%), neutropenia (64%), and white blood cell count decreased (64%). The hematologic AEs are similar to those seen in other pts treated with iopofosine I 131 and are considered predictable and manageable. Enrollment in the Part B expansion for pts with HGG or ependymoma is ongoing. Citation Format: Sameer Farouk Sait, Jennifer H Foster, Daniel A Morgenstern, Scott Raskin, Laura Klesse, Julia Glade-Bender, Kate Oliver, Jarrod Longcor, Nicholas Pytel. Precision radiotherapy for incurable brain tumors: Phase 1b dose & regimen optimization study of iopofosine I 131 in inoperable relapsed or refractory pediatric high-grade glioma, interim data assessment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr A019.