Research led by The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have developed a novel drug that shows to extend survival time for patients with glioblastoma, the most common primary brain tumor in adults.
Results of the study, sponsored by Plus Therapeutics, a clinical-stage pharmaceutical company, where published in the March 7, 2025 edition of Nature Communications. [1]
Glioblastoma, also known as glioblastoma multiforme or GBM, is a highly aggressive and malignant brain tumor. It is the most common primary brain tumor in adults. Today, survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics.
Rhenium Obisbemeda
Results of a trial led by The University of Texas Health Science Center at San Antonio revealed that a unique investigational drug formulation called Rhenium (186Re)* Obisbemeda (186RNL), chelated-186Re encapsulated in nanoliposomes** and delivered to brain tumors via convection enhanced delivery or CED more than doubled median survival and progression-free time, compared with standard median survival and progression rates, and without dose-limiting toxic (DLT) effects.[2]
Improving drug delivery using CED
Results from a variety of studies suggests that most of these therapeutics do not reach their intended targets in the brain when administered via conventional routes (intravenous or oral).
Rhenium Obisbemeda is being delivered using convection enhanced delivery or CED, a relatively novel technology which uses a catheter to deliver a continuous flow of drugs directly to the brain. It involves implanting catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low-positive-pressure bulk flow. Ongoing pre-clinical studies and studies in a clinical setting have shown that CED produced effective delivery of therapeutics to substantial volumes of brain and brain tumor.
“As a disease with a pattern of recurrence, resistance to chemotherapies and difficulty to treat, glioblastoma has needed durable treatments that can directly target the tumor while sparing healthy tissue,” said Andrew J. Brenner, MD, PhD, professor and chair of neuro-oncology research with Mays Cancer Center at UT Health San Antonio.
Brenner is also clinical investigator for the Institute for Drug Development at UT Health San Antonio and co-leader of its Experimental and Development Therapeutics Program, is lead author of the trial’s study published in Nature Communications.[1]
“This trial provides hope, with a second phase under way and planned for completion by the end of this year.”
Brenner noted that the median overall survival time for patients with glioblastoma after standard treatment fails with surgery, radiation and chemotherapy is only about 8 months. More than 90% of patients have a recurrence of the disease at its original location.
Rhenium Obisbemeda enables very high levels of a specific activity of rhenium-186 (186Re), a beta-emitting radioisotope, to be delivered by tiny liposomes, referring to artificial vesicles or sacs having at least one lipid bilayer.
The researchers used a custom molecule known as N,N-bis (2-mercaptoethyl)-N’,N’-diethylethylenediamine (BMEDA) to chelate or attach 186Re and transport it into the interior of a liposome where it is irreversibly trapped.
Phase 1 Study
In this trial, known as the phase 1 ReSPECT-GBM trial^^, scientists set out to determine the maximum tolerated dose of the drug, as well as safety, overall response rate, disease progression-free survival and overall survival.
After failing one to three therapies, 21 patients who were enrolled in the study between March 5, 2015, and April 22, 2021, were treated with the drug administered directly to the tumors using neuronavigation and convection catheters.
The researchers observed a significant improvement in survival compared with historical controls, especially in patients with the highest absorbed doses, with a median survival and progression-free time of 17 months and 6 months, respectively, for doses greater than 100 gray (Gy), referring to units of radiation.
Importantly, they did not observe any dose-limiting toxic effects, with most adverse effects deemed unrelated to the study treatment.
“The combination of a novel nanoliposome radiotherapeutic delivered by convection-enhanced delivery, facilitated by neuronavigational tools, catheter design and imaging solutions, can successfully and safely provide high absorbed radiation doses to tumors with minimal toxicity and potential survival benefit,” Brenner said.
Orphan Drug Designation
This week the U.S. Food and Drug Administration (FDA) also granted Orphan Drug Designation (ODD) to Rhenium Obisbemeda for the treatment of leptomeningeal metastases in patients with lung cancer.
“Receiving Orphan Drug Designation for Rhenium Obisbemeda marks a significant milestone in our efforts to develop a much-needed therapy for lung cancer patients with leptomeningeal metastases,” explained Mike Rosol, Ph.D., Plus Therapeutics Chief Development Officer.
“These patients currently have limited treatment options, and the growing incidence of LM in lung cancer underscores the urgency for new therapies. This designation, in combination with our previously granted Fast Track designation, strengthens our pathway toward delivering an innovative, targeted radiotherapeutic solution for this highly underserved patient population.”
The FDA grants ODD status to an investigational drug or biologic intended to prevent, diagnose, or treat a rare disease or condition affecting fewer than 200,000 people in the United States. The ODD status provides certain benefits to drug developers, including seven potential years of market exclusivity, tax credits for qualified clinical trials, and exemptions from significant regulatory fees, including the Prescription Drug User Fee Act (PDUFA) charge of US $ 4.3 million in 2025 and the Pediatric Research Equity Act (PREA) requirements.
This milestone follows the recent completion of the ReSPECT-LM Phase 1 single-dose trial, which established the recommended Phase 2 dose (RP2D).
The Company is now advancing a Phase 2 single-dose expansion trial and a Phase 1 multiple-dose trial while actively engaging the FDA to define the optimal pivotal trial strategy.
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Note: * Rhenium (186Re) Obisbemeda (186RNL) is being developed by Plus Therapeutics for the treatment of recurrent glioblastoma (GBM), leptomeningeal metastases (LM)^, and pediatric brain cancers (PBCs), including ependymoma and high-grade glioma. For patients diagnosed with glioblastoma and pediatric brain cancers, the size of our nanoliposome is paired with CED-deliverty, which allows the investigationa drug to bypass the blood-brain barrier and enhance drug distribution to a target region. Patients diagnosed with with leptomeningeal metastases receive the investigational drug directly in the CNS compartment (where the tumor is located) intraventricularly via Ommaya reservoir.
** Rhenium (186Re) is a radioactive isotope that emits beta energy with a short half-life (between 17 to 90 hours). The energy submitted has an average energy of 784 keV and a maximum energy of 2.12 MeV, this is sufficient to penetrate and destroy targeted abnormal (e.g. tumor) tissues. In addition, the low-abundant gamma emission of 155 keV (15%) is efficient for imaging and for dosimetric calculations. Rhenium (186Re) is nuclear reactor-produced 1.8 mm average radiation path length of beta energy, while Rhenium (186Re) is generator-produced for quick availability 3.1 mm average radiation path length of beta energy.[2]
^Leptomeningeal metastases (LM), which are also known as leptomeningeal carcinomatosis, is a late-stage cancer complication in which cancer cells spread from four primary cancers – breast, lung, melanoma and gastrointestinal – to the CNS. It is usually found in either the leptomeninges or cerebrospinal fluid (CSF) and often goes undiagnosed due to a lack of symptoms. The disease causes neurological complications including difficulty thinking, double vision, and headaches. The goal of the current standard of care (SOC) is to improve survival and to maintain health related Quality of Life (hrQoL) by delaying neurological deterioration.
^^The 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 US $ 17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT).
Clinical Trials
Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioma (ReSPECT) – ClinicalTrials.gov ID NCT01906385 (The ReSPECT-GBM trial is actively enrolling patients. For more information, follow the link).
Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases (ReSPECT-LM) – ClinicalTrials.gov ID NCT05034497
Reference
[1] Brenner, A.J., Patel, T., Bao, A. Phillips WT, Michalek JE, Youssef M, Weinberg JS, Matsuoka CK, Hedrick MH, LaFrance N, Moore M, Floyd JR Convection enhanced delivery of Rhenium (186Re) Obisbemeda (186RNL) in recurrent glioma: a multicenter, single arm, phase 1 clinical trial. Nat Commun 16, 2079 (2025). https://doi.org/10.1038/s41467-025-57263-1 [Link to Article]
[2] Lepareur N, Lacœuille F, Bouvry C, Hindré F, Garcion E, Chérel M, Noiret N, Garin E, Knapp FFR Jr. Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives. Front Med (Lausanne). 2019 Jun 14;6:132. doi: 10.3389/fmed.2019.00132. PMID: 31259173; PMCID: PMC6587137.
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DOI
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