Plus Therapeutics, Inc. announced treatment of the first patient in Part B (Cohort 4) of the ReSPECT-LM Phase 1/2a dose escalation clinical trial of rhenium (186Re) obisbemeda for the treatment of leptomeningeal metastases (LM) from solid tumors. The maximum total radiation activity administered in Phase 1/Part A was 26.4 millicuries (mCi). In Phase 1/Part B the maximum administered total radiation activity will be 110.0 mCi in cohort 7. Positive data from Part A (Cohorts 1-3) of the ReSPECT-LM clinical study evaluating the Company?s lead radiotherapeutic, rhenium (186Re) obisbemeda, for the treatment of LM were presented at the Society for Neuro Oncology (SNO)/American Society of Clinical Oncology (ASCO) Central Nervous System (CNS) Cancer Conference in August 2023.

In summary, the findings in the Phase 1/Part A showed: Ten patients were treated with a maximum absorbed dose of 85 Gray (Gy) and up to 26.4 mCi of radiation activity. No dose limiting toxicities have been observed and a maximum tolerated dose or maximum feasible dose has not been reached in Part A. Cerebrospinal fluid (CSF) tumor cell counts, evaluated using a molecular diagnostic assay, decreased an average of 53% measured at 28 days post-treatment. In addition, five of the 10 treated patients in Part A remain alive with a median overall survival of 10 months.

The FDA has granted Fast Track designation to rhenium (186Re) obisbemeda for the treatment of LM. The ReSPECT-LM clinical trial is funded, in part, by a 3-year, $17.6 million grant by the Cancer Prevention & Research Institute of Texas. 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. Rhenium (186Re) obisbemeda is a novel injectable radiotherapy specifically formulated to directly deliver targeted high-dose radiation in CNS tumors in a safe, effective, and convenient administration. Rhenium (186Re) obisbemeda has the potential to reduce 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).