Plus Therapeutics, Inc., a clinical-stage pharmaceutical company focused on targeted radiotherapeutics for central nervous system (CNS) cancers, has announced the initiation of the ReSPECT-LM dose optimization trial for REYOBIQ™ (rhenium Re186 obisbemeda). This trial aims to establish the optimal dosing schedule for a potential registrational study in patients with leptomeningeal metastases (LM), a severe complication of advanced cancer affecting the CNS fluid-lined structures. LM is a rare but severe complication of advanced cancer, occurring in approximately 5% of metastatic cancer patients, most commonly from breast cancer, lung cancer, and melanoma. Patients typically have a median survival of only 2-6 months, underscoring the urgent need for more effective treatments.

The decision to proceed with this dose optimization trial follows encouraging results from the Company's completed single-dose escalation trial. The new study is designed to evaluate multiple-dose regimens of REYOBIQ, administered at defined intervals via an intraventricular catheter (Ommaya reservoir). The trial's primary objective, consistent with the FDA's Project Optimus, is to determine the safety and tolerability of these multiple doses and to identify both the maximum tolerated dose and minimum effective dose for LM patients from any primary solid tumor cancer.

The trial plans to enroll up to 24 patients. REYOBIQ will be administered at the recommended Phase 2 dose (RP2D) of 44.1 mCi, fractionated across three dosing intervals (56 days, 28 days, and two 14-day cohorts, one with 6 doses), with up to six patients per cohort interval. Beyond safety, the trial will assess pharmacokinetics/dosimetry and efficacy-related endpoints, including objective response rate (ORR), neurologic progression-free survival (PFS), overall survival (OS), and changes in neurologic status. Furthermore, the trial will analyze cerebrospinal fluid (CSF) tumor cell counts using Plus Therapeutics' CNSide CSF assay platform, along with other pharmacodynamic markers, and compare these findings to standard CSF cytology.

To ensure efficient enrollment, the trial will initially be limited to two high-enrolling cancer centers in Texas: the University of Texas Health Science Center at San Antonio (UTHSCSA) and the University of Texas Southwestern Medical Center (UTSW). Additional sites may be added if necessary.

The dose optimization study builds upon promising data from the previous single-dose escalation trial. Plus Therapeutics plans to present these data and additional information from the completed single-dose escalation trial at the upcoming SNO/ASCO CNS Metastases Conference in August 2025. The Company will also seek an End of Phase 1 Type B meeting with the FDA to align on the clinical development plan and the design for a potential registrational trial. The ReSPECT-LM dose optimization trial is significantly supported by a $17.6 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT), which is the world's second-largest public funding source for cancer research.