Wednesday, September 06, 2023
Plus Therapeutics, Inc. (Nasdaq: PSTV) has officially initiated treatment for the first patient in Part B (Cohort 4) of the ReSPECT-LM Phase 1/2a clinical trial, which focuses on dose escalation. The trial aims to assess the effectiveness of rhenium (186Re) obisbemeda in treating leptomeningeal metastases (LM) originating from solid tumors.
Dr. Norman LaFrance, Chief Medical Officer at Plus Therapeutics, expressed optimism about the Phase 1/Part A findings of the ReSPECT-LM trial. He stated that in Phase 1/Part B, they plan to incrementally increase the dosage to the maximum tolerated single dose while simultaneously working closely with the U.S. Food and Drug Administration (FDA) to introduce multiple dosing strategies into the trial.
In Phase 1/Part A, the maximum total radiation activity administered was 26.4 millicuries (mCi). In Phase 1/Part B, the maximum administered total radiation activity is set to reach 110.0 mCi in cohort 7.
Positive outcomes from Part A (Cohorts 1-3) of the ReSPECT-LM clinical study, evaluating the primary 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 held in August 2023.
Ten patients received treatment with a maximum absorbed dose of 85 Gray (Gy) and radiation activity of up to 26.4 millicuries (mCi).No instances of dose-limiting toxicities were observed, and there was no determination of either a maximum tolerated dose or a maximum feasible dose in Part A.The assessment of cerebrospinal fluid (CSF) tumor cell counts, conducted using a molecular diagnostic assay, indicated an average reduction of 53% at 28 days post-treatment.Furthermore, five out of the ten patients treated in Part A are still alive, with a median overall survival of 10 months. Additionally, it's important to note that the FDA has granted Fast Track designation to rhenium (186Re) obisbemeda for the treatment of leptomeningeal metastases. The ReSPECT-LM clinical trial is supported, in part, by a 3-year, $17.6 million grant from the Cancer Prevention & Research Institute of Texas.
Leptomeningeal metastases (LM) is a rare complication associated with cancer, where the primary cancer spreads to the cerebrospinal fluid (CSF) and the leptomeninges that surround the brain and spinal cord. LM can occur in various malignancies, including solid tumors, primary brain tumors, or hematological malignancies. The most commonly associated cancer with LM is breast cancer, affecting approximately 3-5% of breast cancer patients. Additionally, other cancers like lung cancer, gastrointestinal (GI) cancers, and melanoma can also metastasize to the CSF, resulting in LM.
LM is a challenging condition, affecting approximately 5% of cancer patients, and is typically considered terminal. The prognosis is grim, with a 1-year survival rate of only 7% and a 2-year survival rate of just 3%. The incidence of LM is on the rise, partly due to improved survival rates among cancer patients and partly because many standard chemotherapy treatments cannot effectively reach the required concentrations in the spinal fluid to combat tumor cells. Unfortunately, there are currently no FDA-approved therapies designed specifically for LM patients, and those with untreated LM often face a rapid decline, succumbing to the condition within weeks to several months.
Rhenium (186Re) obisbemeda is an innovative injectable radiotherapy treatment specially formulated to deliver precise, high-dose radiation directly to central nervous system (CNS) tumors, ensuring safety, efficacy, and convenience for patients. This therapy shows potential in reducing risks and improving outcomes for CNS cancer patients compared to existing approved treatments, offering a more targeted and potent radiation dose.
Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, which minimizes radiation exposure, its beta energy that effectively targets and destroys cancerous tissue, and its gamma energy that enables real-time imaging during treatment.
Rhenium (186Re) obisbemeda is currently under investigation for the treatment of recurrent glioblastoma in the ReSPECT-GBM clinical trial, which is supported by a grant from the National Cancer Institute (NCI), a part of the U.S. National Institutes of Health (NIH). It is also being studied for the treatment of leptomeningeal metastases in the ReSPECT-LM clinical trial, funded by a three-year, $17.6 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT).