Plus Therapeutics Updates ReSPECT-GBM Trial at 2024 CNS Annual Meeting

Plus Therapeutics, Inc., a clinical-stage pharmaceutical company, has provided an update on its ongoing ReSPECT-GBM Phase 1/2 clinical trial. The trial is evaluating the company’s primary drug candidate, Rhenium (186Re) Obisbemeda, for the treatment of recurrent glioblastoma. This update was presented at the 2024 Congress of Neurological Surgeons Annual Meeting in Houston, Texas.

Dr. John Floyd, the lead investigator and a neurosurgeon at the University of Texas Health Science Center San Antonio, delivered the presentation. It was titled “Treatment of Recurrent Glioblastoma (rGBM) via Convection Enhanced Delivery (CED) with Rhenium (186Re) Obisbemeda (Rhenium-186 Nanoliposome, 186RNL): ReSPECT-GBM Phase 1/2 Trial Update.” The data presented highlighted the ongoing favorable safety profile and potential efficacy of Rhenium (186Re) Obisbemeda in treating patients with recurrent glioblastoma, a patient group known for its poor prognosis.

The ReSPECT-GBM Phase 1/2 trial is an open-label study that aims to investigate the feasibility, dose escalation, and critical parameters of convection enhanced delivery (CED) for Rhenium (186Re) Obisbemeda in adult patients with recurrent glioblastoma. The study is designed to determine the maximum tolerated dose (MTD), the maximum feasible dose (MFD), safety, and potential efficacy of the drug.

Key findings from this trial update are as follows:

- To date, 42 patients have been enrolled at three sites, and 19 of these have been treated with the recommended Phase 2 dose of 22.3 mCi in 8.8 mL for tumors of approximately 20 cm³ or less.
- All Phase 2 patients had recurrent, histologically confirmed glioblastoma, with single tumors of approximately 20 cm³ or less.
- The average tumor size in Phase 2 was 7.5 mL, with a range between 0.9 and 22.8 mL.
- Increases in absorbed dose were found to correlate with specific drug delivery parameters, such as infused dose, volume, convection flow rate, and the number of catheters used.
- The average absorbed radiation dose to the tumor in Phase 2 was 300 Gy, with 89% of patients meeting the key drug delivery parameters correlating with overall survival, achieving a tumor absorbed dose of over 100 Gy and radiation coverage of more than 70%.
- Out of the 42 enrolled patients, one dose-limiting toxicity (hemiplegia) was reported in Cohort 8 at a dose of 41.5 mCi and 16.3 mL.
- Most adverse events in Phase 2 patients were mild (73.5%) or moderate (18.8%), largely unrelated (37.7%), or unlikely related (27.1%) to the drug. Of the nine severe adverse events reported, only two were related to the study drug.

The trial also revealed that a statistically significant reduction in the tumor volume rate change was seen in tumors that received an absorbed dose of more than 100 Gy. Tumor coverage was found to correlate with tumor control, while regrowth occurred outside the treated areas.

Dr. Marc H. Hedrick, President and CEO of Plus Therapeutics, expressed optimism about the study's progress. He noted that the addition of new clinical trial sites, including North Shore University in New York and Ohio State University in the Upper Midwest, would help in the completion of both the Phase 1 and Phase 2 arms in the near future.

Glioblastoma, affecting about 15,000 people annually in the U.S., is the most common and deadly form of brain cancer. The average life expectancy with glioblastoma is less than 24 months. There is currently no clear standard of care for recurrent glioblastoma, and existing treatments offer only marginal survival benefits with significant side effects.

Rhenium (186Re) Obisbemeda is a novel injectable radiotherapy designed to deliver high dose radiation directly to central nervous system tumors safely and effectively. It aims to reduce off-target risks and improve patient outcomes compared to existing therapies. The drug is also being evaluated for the treatment of leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM clinical trials.

Plus Therapeutics is dedicated to developing targeted radiotherapeutics for difficult-to-treat cancers of the central nervous system, enhancing clinical outcomes through advanced platform technologies and strategic partnerships.