Following positive data from the phase 1 ReSPECT-GBM trial, the first patient has been dosed with rhenium (186Re) obisbemeda in the phase 2 portion.
Trial Name: A Dual Phase 1/2, Investigator Initiated Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of 186Rhenium Nanoliposomes (186RNL) in Recurrent Glioma (CTRC# 12-02)
ClinicalTrials.gov Identifier: NCT01906385
Sponsor: Plus Therapeutics
Recruitment Contact: Melissa Moore, PhD, 347-570-3338, MMoore@plustherapeutics.com and Norman LaFrance, MD, (CMO)215-808-0955, nlafrance@plustherapeutics.com
Completion Date: January 2025
The phase 2 ReSPECT-GBM trial (NCT01906385) of rhenium (186Re) obisbemeda has dosed its first patient with recurrent glioblastoma (GBM), according to Plus Therapeutics, Inc.1
Part 2 of the trial follows the announcement of positive data presented at the Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology in November 2022. In part 1 of ReSPECT-GBM, 24 patients with recurrent GBM were treated with a single dose of 186Re (range, 1.0 mCi/0.66 mL-31.2 mCi/12.3 mL). This reached up to 740 Gray (Gy) of absorbed radiation dose to the tumor.
Each of the patients had astatistically significant improvement in overall survival correlating with the average absorbed dose of radiation to the tumor as well as the percent volume of tumor treated. Specifically, the 100 Gy increase in the absorbed dose led to a 35.7% decrease in the risk of death with a hazard ratio of .643 (P = .003), and a 1% increase in tumor volume treated correlated with a 4.5% decrease in the risk of death (P = .002) and a hazard ratio of .955.2
Overall, findings deemed the treatment to be safe and well-tolerated as there were no dose limiting toxicities.2 The recommended phase 2 dose of 22.3 mCi in 8.8 mL will now be evaluated for tumor volumes of 20 mL or less in an additional 31 patients with GBM and a continued dose-escalation will be performed to assess and treat tumors larger than 20 mL.
Moreover, the FDA granted an orphan drug designation and a fast track designation to the agent for the treatment of patients with GBM.1
“In the phase 1/2a dose escalation trial, we showed that a [186Re] radiation dose of 22.3 mCi in an infused volume of 8.8 mL can be safely administered and that there is a statistically significant correlation between overall survival and both absorbed radiation dose to the tumor and percent tumor volume in the treated volume,” said Andrew J. Brenner, MD, PhD, professor of medicine, neurology, and neurosurgery, Kolitz/Zachry endowed chair neuro-oncology research, and co-leader of the experimental and developmental therapeutics program at The University of Texas Health Science Center at San Antonio, and principal investigator of the ReSPECT-GBM clinical trial, in a press release. “The strength of this correlation is unusually positive for a phase 1/2a trial and we are optimistic that these safety and efficacy signals will be confirmed in the ongoing phase 2b trial.”
ReSPECT-GBM is a phase 2, multi-center, dose-expansion trial designed to evaluate the safety and tolerability of treatment with 186Re. Patients with recurrent GBM that has progressed after conventional treatment will be administered an infusion of the study agent directly into the tumor via convection-enhanced delivery catheters. The starting absorbed dose is 1 mCi in a volume of 0.660 mL.3
The dose-escalation portion of the trial will be followed by an expansion phase where investigators will determine the maximum tolerated dose (MTD) and efficacy of the agent. Up to 31 patients with small- to medium-sized tumors that are 20 mL or less in approximately 24 months are expected to be enrolled in the trial.
Primary end points of the trial include to determine the MTD and overall survival of 186Re. Secondary end points will consist of dose distribution, response rate, survival, and safety of single dose treatment for part 1 of the trial, and safety, tolerability, objective response rate, progression-free survival, and quality-of-life in part 2.
Patients included in the study will be those at least 18 years of age with histologically confirmed grade III/IV recurrent glioma who have progression by a clinically accepted neuro-oncology evaluation, following standard treatment options with known survival benefit for any recurrence, an ECOG performance status of 0-2, and a Karnofsky performance status ≥ 60. Other requirements include to have a life expectancy of at least 2 months, and an acceptable liver, renal, and hepatic function.
If a patient receives treatment with antiepileptic medications, they must have a 2-week history of stable dose without seizures prior to the start of the study. For patients administered corticosteroids to control cerebral edema, they must be maintained at a stable or decreasing dose for a minimum of 2 weeks without progression of clinical symptoms prior to study start.
The study is currently enrolling patients in Texas and has an estimated study completion date of January 2025.
