Plus Therapeutics’ REYOBIQ™ Shows Clinical Benefit and Safety in the ReSPECT-LM Clinical Trial for Patients with Leptomeningeal Metastases (LM)

Rhea-AI Summary

Plus Therapeutics (NASDAQ: PSTV) presented new data for REYOBIQ™ (rhenium Re186 obisbemeda) from its Phase 1 ReSPECT-LM trial for Leptomeningeal Metastases (LM) at the 2025 Nuclear Medicine and Neurooncology Conference. Key findings include:

The trial demonstrated significant clinical benefits with a 76% Clinical Benefit Rate (13/17 patients showing partial response or stable disease) and 87% clinical response rate based on physician evaluation. The treatment showed dose-dependent effectiveness, reaching 253Gy in Cohort 5.

Notably, 5 out of 7 patients who showed >80% reduction in LM tumor cells survived at least one year after initial treatment, with three receiving additional treatment under compassionate use. RNA sequencing revealed early tumor cell death and enhanced immune response, while maintaining a favorable safety profile with limited dose-limiting toxicities.

Positive

• 76% Clinical Benefit Rate (13/17 patients) showing partial response or stable disease
• 87% clinical response rate based on physician evaluation
• 5 out of 7 patients with >80% tumor cell reduction survived at least one year
• RNA sequencing showed positive mechanism of action with early tumor death and immune response
• Multiple doses possible under compassionate use, suggesting potential for long-term treatment

Negative

• Grade 4 dose-limiting toxicity (thrombocytopenia) observed in Cohorts 5 and 6

Insights

Oncology Clinical Trial Specialist

REYOBIQ shows promising clinical benefit in leptomeningeal metastases with 76% clinical benefit rate and long-term survivors among retreated patients.

Plus Therapeutics has presented compelling new data for REYOBIQ™ (rhenium Re186 obisbemeda) in treating leptomeningeal metastases (LM), a rare and devastating condition where cancer spreads to the fluid and tissues surrounding the brain and spinal cord. The results from their Phase 1 ReSPECT-LM trial demonstrate several important clinical outcomes.

The data shows a dose-dependent therapeutic effect, with absorption reaching an impressive 253Gy in the highest cohort. Among the 17 patients with available neuroimaging data, 5 patients (29%) achieved partial responses and 8 patients showed stable disease, yielding a clinical benefit rate of 76%. This is particularly significant for LM, which typically has a dismal prognosis with median survival often measured in weeks to a few months.

What's most striking about this data is the durability of response. Of seven patients who showed greater than 80% reduction in LM tumor cells in cerebrospinal fluid, five survived at least one year after initial treatment. Three of these patients received compassionate use retreatment, suggesting that REYOBIQ might be effectively administered as a repeated therapy.

The mechanistic data is equally impressive, with RNA sequencing revealing early induction of apoptosis (programmed cell death) followed by both innate and adaptive immune responses by Day 28. This dual mechanism—direct tumor cell killing plus immune activation—suggests REYOBIQ may offer advantages over conventional therapies.

Safety appears manageable with dose-limiting toxicity (thrombocytopenia) only observed at the highest dose cohorts (5 and 6), indicating a favorable therapeutic window. For a condition with few effective treatment options, these results represent meaningful progress toward addressing a significant unmet medical need.

Multiple long-term LM survivors in those patients receiving multiple doses of REYOBIQ

RNA sequencing data show early tumor apoptosis and activation of innate immune responses

Updated ReSPECT data presented at the 2025 Nuclear Medicine and Neurooncology Conference

HOUSTON, May 14, 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 the presentation of new data on its lead drug REYOBIQ™ (rhenium Re¹⁸⁶ obisbemeda) during both an oral presentation and a poster presented at the Nuclear Medicine and Neurooncology Conference. The meeting was held May 9-10, 2025 in Vienna, Austria.

"This newly presented data shows safety, clinical benefit and data supporting the underlying mechanism of action for REYOBIQ in patients with Leptomeningeal Metastases," said Marc H. Hedrick, M.D., Plus Therapeutics President and Chief Executive Officer. "Furthermore, multiple doses of REYOBIQ were administered under compassionate use, mirroring how REYOBIQ may one day be used post approval and can contribute to long term survival in LM.”

The study, titled, “Rhenium Obisbemeda (REYOBIQ) in Leptomeningeal Metastases,” highlights additional data from the Company’s now complete Phase 1 ReSPECT-LM dose escalation trial. The presented data added further detail to the previously reported data from the submitted abstract, which demonstrated:

• Dose dependent increase in the average absorbed dose to the cranial and spinal subarachnoid space reaching 253Gy in Cohort 5
• Neuroimaging response data was available for 17 patients as of the data cutoff with five of those (29%) showing a partial response
• An additional eight patients showed stable disease by neuroimaging through day 112 for a Clinical Benefit Rate (complete response + partial response + stable disease) of 76% (13/17 – five partial responses and eight stable disease). Additionally, 87% of subjects demonstrated clinical response based on the physician evaluation (13/15 – 2 response and 11 stable disease)
• No dose limiting toxicity (DLT) observed in the first four cohorts, with a grade 4 DLT (thrombocytopenia), one in each of Cohorts 5 and 6
• RNA sequencing of LM cells showed early induction of apoptosis, with an innate immune response followed by an increase in T cells and an adaptive immune response by Day 28.
• In addition, of the seven patients who received a response of better than 80% in reduction of LM tumor cells in the cerebrospinal fluid, five survived at least one year following initial treatment.
• The study reports that three of those five were retreated via compassionate use.
  

Further details from the poster can be found here.

About Leptomeningeal Metastases (LM)
LM is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. Additionally, lung cancer, GI cancers and melanoma can also spread to the CSF and result in LM. LM occurs in approximately 5% of people with cancer and is usually terminal with 1-year and 2-year survival of just 7% and 3%, respectively. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells, yet there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months, if untreated.

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 and leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM 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).

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://plustherapeutics.com/.

Investor Contact

CORE IR
investor@plustherapeutics.com

FAQ

What are the key clinical results of PSTV's REYOBIQ Phase 1 trial for Leptomeningeal Metastases?

The trial showed a 76% Clinical Benefit Rate, with 5 partial responses and 8 stable disease cases out of 17 patients. Additionally, 87% of subjects demonstrated clinical response based on physician evaluation.

What is the survival rate for PSTV's REYOBIQ treatment in LM patients?

Among patients who showed >80% reduction in LM tumor cells in cerebrospinal fluid (7 patients), 5 survived at least one year following initial treatment, with 3 receiving additional treatment under compassionate use.

What are the side effects of PSTV's REYOBIQ treatment in the Phase 1 trial?

The treatment showed a favorable safety profile with no dose-limiting toxicities in the first four cohorts. However, grade 4 thrombocytopenia was observed as a dose-limiting toxicity in Cohorts 5 and 6.

How does PSTV's REYOBIQ work against Leptomeningeal Metastases?

RNA sequencing showed REYOBIQ induces early tumor cell death (apoptosis), triggers an innate immune response, and leads to increased T cells and adaptive immune response by Day 28.

What was the maximum radiation dose achieved in PSTV's REYOBIQ trial?

The trial demonstrated a dose-dependent increase in absorbed dose to the cranial and spinal subarachnoid space, reaching 253Gy in Cohort 5.