Single intrathecal dose of Rhenium (186Re) Obisbemeda shows a favorable response rate and median overall survival in leptomeningeal metastases (LM) patients
Achieves up to 8x absorbed radiation dose to the CNS subarachnoid space vs. standard of care external beam radiation
Receives FDA agreement to initiate the ReSPECT-LM Phase 1 multiple administration dose escalation trial of Rhenium (186Re) Obisbemeda for LM
AUSTIN, Texas, Nov. 25, 2024 (GLOBE NEWSWIRE) -- 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, presented data updating the progress of its ReSPECT-LM Phase 1 clinical trial of Rhenium (186Re) Obisbemeda (Rhenium Nanoliposome, 186RNL) in leptomeningeal disease (LM). The data were presented at the 2024 Society for Neuro-Oncology (SNO) Annual Meeting November 21-24 in Houston, Texas.
“The combination of a high absorbed radiation dose, favorable safety profile, and consistent response data is very encouraging, particularly in a Phase 1 trial,” said Dr. Andrew Brenner, M.D., Ph.D. “Furthermore, the observed median overall survival rate and long tail survivors receiving multiple doses via compassionate use are uncommon in LM patients, driving our commitment to move rapidly into dose expansion and multiple-dose trials.”
The data were presented in a session titled, “Rhenium (186Re) Obisbemeda (rhenium nanoliposome,186RNL) for the treatment of leptomeningeal metastases (LM): Summary of the Phase 1 dose escalation study and Phase 2 administered dose selection,” 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
ReSPECT-LM Single Administration Dose Escalation Trial
Overview:
Twenty patients with LM were treated and evaluable through Cohort 5, receiving a single intrathecal dose of Rhenium (186Re) Obisbemeda of up to 66.14 mCi of radiation
Primary cancer diagnosis for the 20 patients with LM included breast cancer (n = 9), non-small cell lung cancer (n = 5), and other primary cancers (n = 6)
Safety:
The safety profile through Cohort 5 was favorable, with 1 dose-limiting toxicity (thrombocytopenia) observed in Cohort 5
Pharmacodynamic and pharmacokinetic analyses indicated that after a single administration, Rhenium (186Re) Obisbemeda remained in the cerebrospinal fluid space for at least 7 days and achieved average absorbed doses of up to 253 Gy to the cranial subarachnoid space in Cohort 5
Response:
The best clinical benefit rate from a single dose of Rhenium (186Re) Obisbemeda, assessed from baseline to day 112, was measured through complete response, partial response, and stable disease across three key metrics:
Circulating tumor cells: 93% (14/15 patients) responded, including 1 complete response and 1 stable case
MRI imaging: 75% (12/16 patients), with 5 responses and 7 stable cases
Clinical Response: 86% (12/14 patients), with 2 responses and 10 stable cases
Median overall survival for Cohorts 1-4 was 9 months, with 6 out of the 16 patients alive at the time of analysis
Three of the 20 patients received up to 3 doses of Rhenium (186Re) Obisbemeda under compassionate use IND, all surviving over 400 days, with one exceeding 30 months
Next steps:
The first patient in Cohort 6 has been treated using a modified dose of 75 mCi
Cohort 6 is anticipated to conclude in Q1 2025
Planning is underway for a Phase 1b single dose expansion cohort trial using the Cohort 4 dose of 44 mCi, which is expected to fully enroll in 2025
Obtained agreement from FDA to begin the ReSPECT-LM multi-administration trial for patients with LM (IND 153715); enrollment is expected to begin in early 2025 at seven U.S. trial sites
The trial will be a two-part study aimed at evaluating the safety, dosing intervals, and efficacy of administering multiple doses of Rhenium (186Re) Obisbemeda to patients with LM
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).
About Plus Therapeutics 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 for patients. Combining image-guided local beta radiation and targeted drug delivery approaches, the Company is advancing a pipeline of product candidates with lead programs in recurrent glioblastoma (GBM) and leptomeningeal metastases (LM). The Company has built a supply chain through strategic partnerships that enable the development, manufacturing, and future potential commercialization of its products. Plus Therapeutics is led by an experienced and dedicated leadership team and has operations in key cancer clinical development hubs including Austin and San Antonio, Texas. For more information, visit https://plustherapeutics.com/.
Cautionary Statement Regarding Forward-Looking Statements This presentation 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 “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. These statements include, without limitation, statements regarding the following: the planned dose expansion and multiple-dose trials of patients with leptomeningeal metastases; the timeline for completing the Company’s leptomeningeal metastases patient Cohort 6; the timeline for commencing the Company’s expansion trial of patients with leptomeningeal metastases; and timeline for the Company’s ReSPECT-LM multi-administration trial of patients with leptomeningeal metastases.
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