Higher-Dose Rhenium-186 Nanoliposome Demonstrates OS Advantage in Recurrent Glioma

Andrew J. Brenner, MD, PhD

Rhenium-186 nanoliposome (186RNL) administered at doses exceeding 100 Gy demonstrated promising safety and efficacy results in patients with recurrent glioma, according to phase 1 findings from the ReSPECT-GBM trial (NCT01906385).

Lead author Andrew J. Brenner, MD, PhD, a neuro-oncologist with Mays Cancer Center at UT Health San Antonio, presented findings at the ESMO Congress 2022 showing that 186RNL extended overall survival (OS) when patients receive at least 100 Gy radiation. The median OS was 22.9 months (95% CI, 8.8-42.3) for those who received at least 100 Gy of 186RNL compared with just 5.6 months (95% CI, 1.6-9.4) for those who received a smaller dose. Median OS for the entire cohort (N = 23) was 9.4 months (95% CI, 5.8-13.2). Three patients in the 100 Gy or higher group remain alive compared with no patients in the lower group.

“Those patients who live longest were the ones who had the highest amount of [tumor] coverage and the highest absorbed doses [of radiation],” Brenner said. “We saw a statistically significant loss of benefit in [those who received the] therapeutic dose vs subtherapeutic [dose]. In cohorts 5 to 7, the therapy dose was achieved in 80% of patients and increasing drug volume and radiation correlated with improved OS.”

186RNL comprises radioactive rhenium-186 placed inside of a nanoliposome and administered by convection-enhanced delivery. The nanoliposomes help carry radiation to tumor cells where the radioisotope then releases radiation to attack those cells directly and sparing normal cells.

Investigators recruited 23 total patients, 65% of whom were male. Patients received an average of 1.6 prior treatments (range, 1-3). Patients were stratified into 8 dose levels ranging from 1.0 mCi to 22.3 mCi. Treatment volume increased from 0.6 mL to 8.8 mL. Mean tumor volume was 8.3 mL and the maximum average absorbed radiation dose to the tumor was 584 Gy.

Five (23%) patients received prior bevacizumab (Avastin). However, bevacizumab exposure was an excluding factor in the final 3 cohorts because investigators noted poor delivery of radiation in the first 5 patients.

Brenner noted that the population had “less than ideal prognostic factors.” Thirteen (57%) had unmethylated MGMT status vs 17% methylated and 26% undeclared. Twenty-one (91%) patients had grade IV disease; 2 (9%) had grade III.

Nineteen (83%) patients had wild-type IDH. Two (9%) patients had mutated IDH and 2 were negative. The average tumor volume was 8.1 cm³ (range, 0.9-22.8).

All patients received computerized treatment planning and placement of up to 4 intracranial catheters. Each patient received a single administration of 186RNL by convection enhanced delivery. Investigators assessed dosimetry and radiation distribution following treatment on days 1 to 8 using whole body planar and SPECT/CT imaging. Patients were followed for safety, sufficiency of radiation delivery, and OS.

Brenner noted that tumor coverage correlated with response. In 1 patient, tumor volume was 6.5 mL and coverage was greater than 90%.

“We saw a little bit of increase in the [tumor] size…through the first 3 months with possible pseudoprogression,” he said. “But by day 362, this had significantly decreased in size and the patient had survival beyond 950 days.”

Investigators observed no dose limiting toxicities and most adverse events (AEs) were grade 1/2. For grade 3 AEs, investigators observed 1 incident of osteonecrosis in the left shoulder, 2 seizures, 2 vasogenic cerebral edemas, and 1 pneumonia.

In his concluding remarks, Brenner noted that no dosing failures were reported and that single-administration with 186RNL resulted in approximately 20 times more absorbtion vs extended beam radiation therapy at 740 Gy vs 35 Gy. A phase 2 trial is anticipated which will evaluate 22.3 mCi in 8.8 mL for patients with recurrent glioma less than 20 mL in total volume.

Giuseppe Minniti, MD, PhD, a clinical associate professor and neuro-oncology consultant with the Department of Neurosciences, Neurosurgery at the University La Sapienza in Rome, Italy, offered perspective on the results. He said many questions remain to be answered including the optimal number of catheters and whether tumor geometry characteristics could affect dose distribution. Nonetheless, he called the findings “very promising.”

“We don’t see often [this] long survival in the [recurrent] setting,” he said. “But it’s quite interesting that there is a significant difference between the survival according to the radiation dose.”

Reference

Brenner AJ, Phillips WT, Bao A, et al. The ReSPECT-GBM™ phase I/IIa trial of rhenium-186 nanoliposome (186RNL) in recurrent glioma via convection enhanced delivery (CED) and planned phase IIb trial. Presented at: ESMO Congress 2022; September 9-13, 2022; Paris, France. Abstract 2770.