On December 17, 2024 Plus Therapeutics, Inc. (Nasdaq: PSTV) ("Plus" or the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system cancers, reported data updating the progress of its ReSPECT-LM Phase 1 clinical trial of Rhenium (186Re) Obisbemeda (Rhenium Nanoliposome, 186RNL) in leptomeningeal disease (LM) with a specific focus on breast cancer patients (Press release, Plus Therapeutics, DEC 17, 2024, View Source [SID1234649162]). The data were presented at the 2024 San Antonio Breast Cancer Symposium on December 10-13.

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The data were presented in a session titled "Rhenium (186Re) Obisbemeda (Rhenium Nanoliposome, 186RNL) for the Treatment of Leptomeningeal Metastases (LM): Update on Phase 1 Dose Escalation Study," by Andrew Brenner, M.D., Ph.D., Professor and Kolitz/Zachry Endowed Chair Neuro-Oncology Research; Co-Leader, Experimental and Developmental Therapeutics Program, University of Texas Health, San Antonio.

Key Highlights from the Presentation:

Nine of 20 patients with LM primary breast cancer were treated and evaluable through five dose escalation cohorts, with the maximum tolerated dose yet to be reached
Primary breast cancer biomarker status across the 9 patients were:
ER positive/HER2 negative: n=3
HER2 positive: n=2
Triple negative: n=4
Patients received a single intrathecal dose of Rhenium (186Re) Obisbemeda, ranging from 6.6 to 66.14 mCi of radiation
Only one dose-limiting toxicity (thrombocytopenia) was reported (Cohort 5)
A linear increase in absorbed dose was observed from Cohorts 1 through 5, with an average absorbed dose of 253 Gy to the cranial subarachnoid space in Cohort 5
Circulating tumor cell (CTC) and radiographic (MRI) response data were available for 8 of the 9 breast cancer patients with LM, and clinical response data were available for 7 of the 9 patients
Best response rates (response only) were:
CTC: 88% (7/8)
MRI imaging: 25% (2/8)
Clinical: 29% (2/7)
Clinical benefit rates (response and stable disease) were:
CTC: 100% (8/8)
MRI imaging: 75% (6/8)
Clinical: 71 % (5/7)
Median overall survival for 9 breast cancer patients was 9 months, with 2 patients surviving beyond 600 days post-treatment
Next steps:

Initiate ReSPECT-LM Phase 1b single-dose breast expansion cohort in Q1 2025 to further evaluate single-dose safety and efficacy of Rhenium (186Re) Obisbemeda
"Breast cancer is the most common primary cancer associated with leptomeningeal metastases," said Marc H. Hedrick, M.D., Plus Therapeutics’ President and Chief Executive Officer. "Based on the promising data observed thus far, we intend to move forward rapidly into a breast cancer focused expansion cohort along with our planned multiple dose expansion trial."

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 Rhenium (186Re) obisbemeda
Rhenium (186Re) 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. Rhenium (186Re) obisbemeda 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. Rhenium (186Re) obisbemeda 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).