Plus Therapeutics Presents Positive ReSPECT-LM Clinical Trial Results of REYOBIQ™ in Leptomeningeal Metastases

Rhea-AI Summary

Plus Therapeutics (NASDAQ:PSTV) announced positive results from its ReSPECT-LM Phase 1 trial for REYOBIQ™ in treating leptomeningeal metastases (LM). The trial, involving 29 subjects across 6 cohorts, demonstrated significant efficacy with a 76% radiographic and 87% clinical response rate through day 112.

Key outcomes include 100% reduction in CSF tumor cells at day 28, with five of seven patients showing >80% tumor cell reduction surviving at least one year. The median overall survival reached 9 months, substantially better than the typical 4-month survival rate. The study established a recommended Phase 2 single dose of 44.1 mCi, with no dose-limiting toxicities in cohorts 1-4 and manageable safety profile in higher doses.

[ "Clinical benefit rate exceeded 75% in 3 key outcome measures", "Median overall survival of 9 months vs typical 4 months in literature", "100% reduction in CSF tumor cells observed at day 28", "Favorable safety profile with majority of adverse events being Grade 1 and 2", "Five of seven patients with >80% tumor cell reduction survived at least 1 year" ]

Positive

• None.

Negative

• One dose-limiting toxicity of grade 4 cytopenia observed in each of cohorts 5 and 6

Insights

Oncology Clinical Trial Expert

PSTV's REYOBIQ shows impressive 76% radiographic response and 9-month median survival in deadly leptomeningeal metastases, significantly outperforming historical outcomes.

The Phase 1 ReSPECT-LM trial results for REYOBIQ (Rhenium Obisbemeda) demonstrate remarkably positive outcomes in a notoriously difficult-to-treat condition. Leptomeningeal metastases typically carry a dismal prognosis with median survival of approximately 4 months. The 9-month median overall survival observed in cohorts 1-4 represents a potentially significant advancement.

The 76% radiographic response rate and 87% clinical response rate through day 112 are particularly noteworthy. Even more compelling is the 100% reduction in CSF tumor cell enumeration at day 28 and the observation that 5 of 7 patients with >80% tumor cell reduction survived at least one year. These metrics suggest meaningful disease control.

The RNA sequencing data provides valuable mechanistic insights, showing early induction of apoptosis (programmed cell death) followed by immune response activation, indicating a multi-modal effect. This suggests REYOBIQ may not only directly kill tumor cells but potentially sensitize them to immune surveillance.

The safety profile appears manageable with no dose-limiting toxicities in cohorts 1-4, and only grade 4 cytopenia (reduction in blood cells) observed in higher dose cohorts. The selection of 44.1 mCi as the recommended Phase 2 dose strikes a balance between efficacy and safety.

The absorption of 272 Gy to the cranial and spinal subarachnoid space in cohort 6 represents substantial radiation delivery to the target area, which is critical for efficacy in radiotherapeutics.

REYOBIQ produced a clinical benefit rate of over 75% in 3 clinically relevant outcome measures

RNA sequencing and circulating tumor cell reduction consistent with tumor cell death

No dose limiting toxicities were observed with an overall favorable safety profile

HOUSTON, Aug. 18, 2025 (GLOBE NEWSWIRE) -- 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, announces positive data from the ReSPECT-LM Phase 1 single dose escalation trial presented at the podium at the SNO/ASCO CNS Metastases Conference in Baltimore, MD. The data demonstrated treatment of leptomeningeal metastases (LM) with REYOBIQ is feasible, has a manageable safety profile, and shows a promising efficacy signal.

The presentation, titled, “Phase 1 Dose Escalation of Rhenium (186Re) Obisbemeda (Rhenium Nanoliposome,186RNL (REYOBIQ) for the Treatment of Leptomeningeal Metastases (LM): Clinical Study Results for Safety and Efficacy,” highlighted study results to date from a total of 29 subjects in cohorts 1 – 6 who received 6.6 mCi, 13.2 mCi, 26.4 mCi, 44.10 mCi, 66.14 mCi, or 75mCi of REYOBIQ, respectively.

Presented Data Highlights:

• Radiographic and clinical response rate of 76% and 87%, respectively, through day 112
• CSF tumor cell enumeration (TCE) assays (CNSide test) showed a maximum reduction over baseline of 100% at day 28
• Five of the 7 patients with a TCE response >80% survived at least 1 year
• RNA sequencing of LM cells showed early induction of apoptosis, with an innate immune response followed by an adaptive immune response by day 28
• Median overall survival of 9 months across cohorts 1-4 (20 patients) months, comparing favorably with literature reports of ~4 months
• No dose-limiting toxicity (DLT) was observed in cohorts 1-4, with 1 DLT in each of cohorts 5 and 6 of grade 4 cytopenia
• The majority of adverse events across the trial were Grade 1 and 2
• Mean absorbed dose to the cranial and spinal subarachnoid space was 272 Gy in cohort 6  
• A recommended phase 2 single dose of 44.1 mCi was determined  
  

“Responses were observed in early cohorts with excellent tolerance at much higher doses supporting a broad therapeutic range,” said Dr. Andrew Brenner, M.D., Ph.D., Professor of Medicine in the Division of Hematology and Oncology at The University of Texas Health Science Center at San Antonio. “Furthermore, the trial gave us exactly what we needed to move into the ongoing dosing optimization trial and then to a potential approval trial.”

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.

About CNSide Diagnostic, LLC
CNSide Diagnostics, LLC is a wholly owned subsidiary of Plus Therapeutics, Inc. that develops and commercializes proprietary laboratory-developed tests, such as CNSide®, designed to identify tumor cells that have metastasized to the central nervous system in patients with carcinomas and melanomas. The CNSide® CSF Assay Platform enables quantitative analysis and molecular characterization of tumor cells and circulating tumor DNA in the cerebrospinal fluid that inform and improve the management of patients with leptomeningeal metastases.

About Plus Therapeutics
Headquartered in Houston, Texas, Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company developing targeted radiotherapeutics for difficult-to-treat cancers of the central nervous system with the potential to enhance clinical outcomes. Combining image-guided local beta radiation and targeted drug delivery approaches, the Company is advancing a pipeline of product candidates with lead programs in leptomeningeal metastases (LM) and recurrent glioblastoma (GBM). The Company has built a supply chain through strategic partnerships that enable the development, manufacturing, and future potential commercialization of its products. For more information, visit https://www.plustherapeutics.com.

Forward-Looking Statements
This press release contains statements that may be deemed “forward-looking statements” within the meaning of U.S. securities laws, including statements regarding clinical trials, expected operations and upcoming developments. All statements in this press release other than statements of historical fact are forward-looking statements. These forward-looking statements may be identified by future verbs, as well as terms such as “expect” “potential,” “anticipating,” “planning” and similar expressions or the negatives thereof. Such statements are based upon certain assumptions and assessments made by management in light of their experience and their perception of historical trends, current conditions, expected future developments and other factors they believe to be appropriate.

The forward-looking statements included in this press release could differ materially from those expressed or implied by these forward-looking statements because of risks, uncertainties, and other factors that include, but are not limited to, the following: the Company’s ability to maintain the listing of its common stock on Nasdaq; risks related to a halt in trading or delisting of the Company’s common stock on Nasdaq; Medicare and private payors may not provide coverage and reimbursement or may breach, rescind or modify their contracts or reimbursement policies or delay payments; the risk that our products and services may not perform as expected; the early stage of the Company’s product candidates and therapies; the results of the Company’s research and development activities, including uncertainties relating to the clinical trials of its product candidates and therapies; the Company’s liquidity and capital resources and its ability to raise additional cash; the outcome of the Company’s partnering/licensing efforts, risks associated with laws or regulatory requirements applicable to it; market conditions, product performance, litigation or potential litigation, and competition within the cancer diagnostics and therapeutics field; ability to develop and protect proprietary intellectual property or obtain licenses to intellectual property developed by others on commercially reasonable and competitive terms; challenges associated with radiotherapeutic manufacturing, production and distribution capabilities necessary to support the Company’s clinical trials and any commercial level product demand; and material security breach or cybersecurity attack affecting the Company’s operations or property. This list of risks, uncertainties, and other factors is not complete. Plus Therapeutics discusses some of these matters more fully, as well as certain risk factors that could affect Plus Therapeutics’ business, financial condition, results of operations, and prospects, in its reports filed with the SEC, including Plus Therapeutics’ annual report on Form 10-K for the fiscal year ended December 31, 2024, quarterly reports on Form 10-Q, and current reports on Form 8-K. These filings are available for review through the SEC’s website at www.sec.gov. Any or all forward-looking statements Plus Therapeutics makes may turn out to be wrong and can be affected by inaccurate assumptions Plus Therapeutics might make or by known or unknown risks, uncertainties, and other factors, including those identified in this press release. Accordingly, you should not place undue reliance on the forward-looking statements made in this press release, which speak only as of its date. The Company assumes no responsibility to update or revise any forward-looking statements to reflect events, trends or circumstances after the date they are made unless the Company has an obligation under U.S. federal securities laws to do so.

Investor Contact
CORE IR
investor@plustherapeutics.com 

FAQ

What were the key results of Plus Therapeutics' (PSTV) ReSPECT-LM trial for REYOBIQ?

The trial showed a 76% radiographic and 87% clinical response rate, with median overall survival of 9 months compared to typical 4 months. A 100% reduction in CSF tumor cells was observed at day 28.

What is the recommended Phase 2 dose for REYOBIQ based on the trial results?

The recommended Phase 2 single dose was determined to be 44.1 mCi, showing excellent tolerance and efficacy.

How many patients were involved in Plus Therapeutics' REYOBIQ trial?

The trial included 29 subjects across 6 cohorts, receiving doses ranging from 6.6 mCi to 75mCi of REYOBIQ.

What was the safety profile of REYOBIQ in the Phase 1 trial?

The majority of adverse events were Grade 1 and 2, with no dose-limiting toxicity in cohorts 1-4. One case of grade 4 cytopenia was observed in each of cohorts 5 and 6.

What was the survival rate for patients with significant tumor cell reduction in the PSTV trial?

Five out of seven patients who showed tumor cell enumeration response greater than 80% survived for at least one year.