A groundbreaking investigational drug has shown remarkable promise in extending survival for patients with glioblastoma, the most aggressive and common primary brain tumor in adults. Research led by The University of Texas Health Science Center at San Antonio (UT Health San Antonio) revealed that Rhenium Obisbemeda (186RNL) more than doubled median survival time in patients with recurrent glioblastoma compared to historical controls.
The findings, published in the March 7, 2025 edition of Nature Communications, represent a significant advancement in the treatment of a disease that has seen little progress despite decades of clinical trials.
Significant Survival Improvement in Phase 1 Trial
The phase 1 ReSPECT-GBM trial enrolled 21 patients between March 2015 and April 2021 who had failed one to three previous therapies. Researchers observed that patients receiving the highest absorbed doses (greater than 100 gray) achieved a median survival of 17 months and progression-free time of 6 months – more than double the typical 8-month survival rate for recurrent glioblastoma patients after standard treatment failure.
"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 Dr. Andrew J. Brenner, lead author of the study and professor and chair of neuro-oncology research with Mays Cancer Center at UT Health San Antonio.
Importantly, the trial demonstrated no dose-limiting toxic effects, with most adverse events deemed unrelated to the treatment.
Innovative Drug Delivery Mechanism
Rhenium Obisbemeda represents a novel approach to treating brain tumors by combining several innovative technologies:
- The drug utilizes rhenium-186 (186Re), a beta-emitting radioisotope with a short half-life (17-90 hours)
- The radioactive material is encapsulated in nanoliposomes – tiny artificial vesicles with lipid bilayers
- Delivery occurs via convection enhanced delivery (CED), using catheters to bypass the blood-brain barrier and deliver the drug directly to brain tumors
This approach addresses a fundamental challenge in brain cancer treatment – most therapeutics administered through conventional routes (intravenous or oral) fail to reach their intended targets in the brain.
"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," Dr. Brenner explained.
Expanding Treatment Applications
The drug's potential extends beyond glioblastoma. The U.S. Food and Drug Administration (FDA) recently granted Orphan Drug Designation (ODD) to Rhenium Obisbemeda for treating leptomeningeal metastases in lung cancer patients.
"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," said Dr. Mike Rosol, Chief Development Officer at Plus Therapeutics, the clinical-stage pharmaceutical company sponsoring the trials.
Leptomeningeal metastases occur when cancer cells from primary tumors – typically breast, lung, melanoma, or gastrointestinal cancers – spread to the central nervous system. The condition is often difficult to diagnose and has limited treatment options.
Clinical Development Progress
The ReSPECT-GBM trial is part of a broader development program for Rhenium Obisbemeda, which also includes:
- A Phase 2 trial for recurrent glioblastoma currently underway and expected to complete by the end of 2025
- The recently completed ReSPECT-LM Phase 1 single-dose trial for leptomeningeal metastases
- An advancing Phase 2 single-dose expansion trial and Phase 1 multiple-dose trial
- Development for pediatric brain cancers, including ependymoma and high-grade glioma
The ReSPECT-GBM program is supported by the National Cancer Institute (NCI), while the ReSPECT-LM program received a three-year $17.6 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT).
Addressing an Urgent Unmet Need
Glioblastoma remains one of the most challenging cancers to treat, with more than 90% of patients experiencing recurrence at the original tumor location. Standard treatment typically involves surgery, radiation, and chemotherapy, but outcomes remain poor.
The promising results from this Phase 1 trial offer new hope for patients facing this devastating diagnosis. As Dr. Brenner noted, "This trial provides hope, with a second phase under way and planned for completion by the end of this year."
The collaborative research effort included UT Health San Antonio, Mays Cancer Center, UT Southwestern Medical Center of Dallas, Case Western Reserve University in Cleveland, and the University of Texas MD Anderson Cancer Center in Houston.
