On June 30, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported the initiation of the ReSPECT-LM dose optimization trial for REYOBIQTM (rhenium Re186 obisbemeda) for the treatment of leptomeningeal metastases (LM) (Press release, Plus Therapeutics, JUN 30, 2025, View Source [SID1234654175]). The dose optimization trial follows encouraging results from the Company’s single-dose escalation trial and is designed to evaluate multiple-dose regimens of REYOBIQ administered at defined intervals via intraventricular catheter (Ommaya reservoir).
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"A safe and effective therapeutic to address the epidemic of CNS metastases and specifically leptomeningeal metastases is urgently needed," said Marc H. Hedrick, M.D., Plus Therapeutics President and Chief Executive Officer. "We expect that optimizing the dosing regimen for REYOBIQ in this trial will provide data needed to design and support a follow-on registrational trial."
ReSPECT-LM Dose Optimization Trial Design
The study design is consistent with the FDA’s Project Optimus, and aims to optimize treatment dosing for maximum efficacy and safety. The primary objectives of the trial include determining the safety and tolerability of multiple REYOBIQ doses administered via intraventricular catheter at defined intervals in patients with LM from any primary solid tumor cancer and to identify both the maximum tolerated dose and minimum effective dose.
Key additional elements of the trial design include:
Enrollment of up to 24 patients, evaluating REYOBIQ administered at the recommended Phase 2 dose or R2PD of 44.1 mCi, fractionated across three dosing intervals, with up to six patients per cohort interval:
Cohort 1: 56 days
Cohort 2: 28 days
Cohort 3a: 14 days
Cohort 3b: 14 days (6 doses)
The trial will evaluate both safety, pharmacokinetics/dosimetry, and select efficacy-related endpoints such as objective response rate (ORR), neurologic progression-free survival (PFS), overall survival (OS), changes in neurologic status
Furthermore, the trial will analyze cerebrospinal fluid (CSF) tumor cell counts via Plus’ CNSide CSF assay platform, other pharmacodynamic markers, and compare these to standard CSF cytology
Because of the anticipated pace of enrollment, the trial is being limited initially to only two prestigious and high enrolling cancer centers, both in Texas—the University of Texas Health Science Center at San Antonio (UTHSCSA) and the University of Texas Southwestern Medical Center (UTSW) but may expand to more sites if needed.
The dose optimization study builds on promising results from the Company’s single-dose escalation trial. Key highlights include:
Cohort 4 dose (44.1 mCi) was determined to be the RP2D
Pharmacodynamic and pharmacokinetic data showed that a single dose of REYOBIQ remained in the CSF for at least 7 days, and delivered up to an average absorbed dose of 253 Gy to the cranial subarachnoid space in Cohort 5
Neuroimaging results showed a clinical benefit rate1 of 76%, with 5 of 17 patients (29%) achieving partial responses and 8 (47%) maintaining stable disease through Day 112
Clinical examination showed a clinical benefit rate in 87% of evaluable patients, with 13 of 15 patients showing a partial response or stable disease based on physician assessment
No dose-limiting toxicities (DLTs) were observed in the first four cohorts; one Grade 4 DLT (thrombocytopenia) occurred in each of Cohorts 5 and 6
Biologic signals of early apoptosis, innate immune activation, and increased T-cell activity by Day 28, as observed through RNA sequencing of LM cells
5 of 7 patients with over 80% reduction of LM tumor cells in CSF survived at least one year after initial treatment
The Company anticipates presenting these data and additional information from the completed single-dose escalation trial at the upcoming SNO/ASCO CNS Metastases Conference on August 14-16, 2025, in Baltimore, MD. The company will also request an End of Phase 1 Type B meeting with the FDA to align on the clinical development plan and the design of a potential registrational trial.
The ReSPECT-LM dose optimization trial benefits from a $17.6 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT), the second largest public funding source for cancer research in the world.
About LM
Leptomeningeal metastases (LM) are a rare but severe complication of advanced cancer, affecting the fluid-lined structures of the central nervous system. LM occurs in approximately 5% of patients with metastatic cancer, with breast cancer, lung cancer, and melanoma being the most common sources. Median survival is typically 2-6 months, and effective treatment options are limited, highlighting the urgent need for novel therapies.
About REYOBIQ (rhenium Re186 obisbemeda)
REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy specifically formulated to deliver direct targeted high dose radiation in CNS tumors in a safe, effective, and convenient manner to optimize patient outcomes. REYOBIQ has the potential to reduce off target risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue, and gamma energy for real-time imaging. REYOBIQ is being evaluated for the treatment of recurrent glioblastoma, leptomeningeal metastases, and pediatric brain cancer in the ReSPECT-GBM, ReSPECT-LM, and ReSPECT-PBC clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT). The Company’s ReSPECT-PBC clinical trial for pediatric brain cancer is supported by a $3 million grant from the U.S. Department of Defense’s Peer Reviewed Cancer Research Program.