ReSPECT Study Shows Positive Results in Recurrent Glioblastoma

The investigational drug Rhenium NanoLiposome (RNL) demonstrated efficacy in an interim analysis presented at the 2020 Society for Neuro-Oncology (SNO) Annual Meeting for patients with recurrent glioblastoma (GBM), according to a press release from Plus Therapeutics, Inc.¹

In the phase 1 ReSPECT trial (NCT01906385), RNL delivered up to 15 times the absorbed dose of radiation versus the standard external beam radiation therapy without significant toxicity. This has led investigators to progress to the sixth dose escalation cohort for patients in the ReSPECT study.

“The results we have seen thus far from ReSPECT are encouraging and support the continued development of RNL as a potential new option for recurrent GBM patients,” Andrew J. Brenner, MD, PhD, Associate Professor of Medicine, Neurology, and Neurosurgery at The University of Texas, Health Services Center at San Antonio and principal investigator of the study, said in a statement. “With limited therapeutic options for these patients, we remain committed to advancing this clinical program to further investigate the therapeutic potential of RNL.”

So far, there was a median survival duration of 4.8 months for the 7 patients receiving RNL who were previously given bevacizumab (Avastin); the 8 patients who were bevacizumab naïve had a median survival of 11.0 months (range, 3.5-33) and a mean survival of 15.4 months (95% CI, 7.4-23.4). Two patients had an overall survival of more than 30 months after receiving RNL, and 4 patients were still alive at the time of the data cut off.

In the first 5 of the 6 planned cohorts, all 15 patients completed treatment. The radiation dose of RNL was successfully increased from 0.66 mL to 8.8 mL, as well as the treatment volume from 1.0 mCi to 22.3 mCi. Patients in cohort 5 received 423 Gy of RNL as the average absorbed radiation dose.

“Treatment for GBM remains a significant challenge as current therapies have exhibited limited efficacy,” Marc Hedrick, MD, president and chief executive officer of Plus Therapeutics, said in a press release. “RNL’s novel design allows the drug to be targeted directly into the tumor using a small catheter and enabling greater control of radiation dosing. These encouraging data reinforce RNL’s potential to deliver targeted high-dose radiation in a safe, effective, and convenient manner.”

In September 2020, an Orphan Drug designation and Fast Track designation were granted by the FDA for this therapy in patients with GBM.^2,3

Investigators observed that RNL was well tolerated in these patients, with no dose-limiting toxicities even though patients absorbed higher doses of radiation compared with external beam radiation therapy.1 Most of the adverse events (AEs) besides scalp discomfort were deemed causally unrelated to RNL; scalp discomfort was thought to be related to the surgical procedure.AEs did not appear to increase in incidence or severity when the dose of RNL went up. Four serious AEs were reported, but none were considered causally related to the study drug.

For the sixth and final dose escalation cohort of ReSPECT, 1 patient has been treated so far and the cohort is expected to have full enrollment by the end of the year.

_References:

_{1. Plus Therapeutics announces positive interim data from ReSPECT™ phase 1 clinical trial in recurrent glioblastoma. News release. Plus Therapeutics. Published November 19, 2020. Accessed November 20, 2020. https://bit.ly/2IU10Wz}

_{2. Plus Therapeutics, Inc. receives FDA Orphan Drug designation for its novel glioblastoma treatment. News release. Plus therapeutics, Inc. September 1, 2020. Accessed November 20, 2020. https://bit.ly/3bjB40N}

_{3. Plus Therapeutics receives Fast Track designation from FDA for its novel glioblastoma treatment. News release. Plus therapeutics, Inc. September 15, 2020. Accessed November 20, 2020. https://bit.ly/36TZ5cU}