The investigational drug formulation rhenium (Re)-186 obisbemeda (RNL-186) may extend survival in patients with glioblastoma, according to a recent study published by Brenner et al in Nature Communications.
Background
Glioblastoma is the most common primary brain tumor in adult patients. The median overall survival among patients with glioblastoma who don’t respond to standard treatment with surgery, radiation, and chemotherapy is about 8 months. Over 90% of patients experience cancer recurrence at its original location.
“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,” stressed lead study author Andrew J. Brenner, MD, PhD, Professor and Chair of Neuro-Oncology Research at the Mays Cancer Center, Co-Leader of the Experimental and Development Therapeutics Program, and a clinical investigator at the Institute for Drug Development at The University of Texas Health Science Center at San Antonio.
“This trial provides hope, with a second phase under way and planned for completion by the end of this year,” he added.
Study Methods and Results
In the phase I ReSPECT-GBM trial, researchers sought to determine the maximum tolerated dose and safety of RNL-186. They also assessed overall response, progression-free survival, and overall survival rates following treatment among 21 patients without response to up to three prior therapies. The patients were enrolled between March 5, 2015, and April 22, 2021, and were administered RNL-186 directly to their tumors using neuronavigation and convection catheters.
The researchers detailed that the nanoliposome radiotherapeutic RNL-186 works by enabling high levels of a specific activity of Re-186—a beta-emitting radioisotope—to be delivered by tiny liposomes, referring to artificial vesicles or sacs having at least one lipid bilayer. They used a custom molecule known as N,N-Bis(2-mercaptoethyl)-N’,N’-diethylethylene diamine to chelate Re-186 and transport it into the interior of a liposome, where it was irreversibly trapped.
The researchers found that the patients who received RNL-186—particularly those with the highest absorbed doses— achieved median and progression-free survival times of 17 months and 6 months, respectively, following doses greater than 100 Gy compared with histologic controls.
Notably, the researchers reported no dose-limiting adverse effects in the RNL-186 group.
Conclusions
“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 concluded.
The researchers are currently recruiting patients for the second phase of the ReSPECT-GBM trial.
Disclosure: For full disclosures of the study authors, visit nature.com.
