Plus Therapeutics presented updated findings from its ReSPECT-GBM Phase 1/2 clinical trial, highlighting the potential of Rhenium (186Re) Obisbemeda in treating recurrent glioblastoma (GBM). The data, presented at the 2024 Congress of Neurological Surgeons (CNS) Annual Meeting, demonstrated a favorable safety profile and encouraging efficacy results for the targeted radiotherapeutic.
The ReSPECT-GBM trial is an open-label study evaluating the feasibility, dose escalation, and convection enhanced delivery (CED) parameters of Rhenium (186Re) Obisbemeda in recurrent adult glioma. The trial aims to determine the maximum tolerated dose (MTD), maximum feasible dose (MFD), safety, and potential efficacy of the drug.
Key Findings from the ReSPECT-GBM Trial
The trial enrolled 42 patients across three sites, with 19 patients receiving the recommended Phase 2 dose of 22.3 mCi in 8.8 mL for tumors ≤20 cm3. All Phase 2 patients had histologically confirmed recurrent glioblastoma. The average tumor size in Phase 2 was 7.5 mL (range 0.9-22.8 mL).
Increases in absorbed dose correlated with drug delivery parameters such as infused dose and volume, maximal convection flow rate, and the number of catheters used. The average absorbed radiation dose to the tumor in Phase 2 was 300 Gy (n=18, 1 patient still under analysis).
Safety and Tolerability
Rhenium (186Re) Obisbemeda demonstrated a favorable safety profile. In Phase 2, most adverse events (AEs) were mild (73.5%) or moderate (18.8%), and largely unrelated (37.7%) or unlikely related (27.1%) to the drug. Of the nine severe adverse events (SAEs), only two were related to the study drug. One dose-limiting toxicity (hemiplegia) was reported in Cohort 8 (41.5 mCi and 16.3 mL).
Efficacy Signals
To date, 88.9% of Phase 2 patients met key CED drug delivery parameters associated with overall survival, achieving a tumor absorbed dose >100 Gy and radiation coverage >70%. Quantitative image analysis revealed a statistically significant reduction in tumor volume rate change in tumors receiving >100 Gy absorbed dose (n=11, p<0.005). Sufficient tumor coverage correlated with tumor control, while regrowth occurred outside treated areas.
Expansion and Future Directions
The ReSPECT-GBM trial has expanded to two new sites at North Shore University in New York and Ohio State University in the Upper Midwest. This expansion aims to facilitate the completion of both Phase 1 and Phase 2 arms of the trial.
According to John Floyd, M.D., lead investigator and neurosurgeon at the University of Texas Health Science Center San Antonio, the trial reinforces the safety signal and potential efficacy of Rhenium (186Re) Obisbemeda in patients with recurrent glioblastoma. He added that the encouraging safety profile and overall survival rates support its advancement as a promising therapeutic option.
Marc H. Hedrick, M.D., President and CEO of Plus Therapeutics, stated that the trial continues to show promising feasibility, safety, response, and potential efficacy. He anticipates that the addition of new clinical trial sites will help complete both the Phase 1 and Phase 2 arms in the near term.
About Glioblastoma
Glioblastoma (GBM) is a highly aggressive and lethal form of brain cancer, affecting approximately 15,000 patients annually in the U.S. The average life expectancy with GBM is less than 24 months, with a one-year survival rate of 40% and a five-year survival rate of around 5%. There is no clear standard of care for recurrent GBM, and current treatments offer only marginal survival benefits with significant side effects.
About Rhenium (186Re) Obisbemeda
Rhenium (186Re) Obisbemeda is an injectable radiotherapy designed to deliver targeted high-dose radiation directly to CNS tumors. It has the potential to reduce off-target risks and improve outcomes for CNS cancer patients due to its targeted and potent radiation dose. The ReSPECT-GBM trial is supported by an award from the National Cancer Institute (NCI), and the ReSPECT-LM trial is funded by a grant from the Cancer Prevention & Research Institute of Texas (CPRIT).
