This article was originally published by Targeted Oncology™. This version has been lightly edited.
Key Takeaways:
- Rhenium (186Re) obisbemeda is a novel injectable radiotherapy that delivers a highly targeted high dose of radiation to central nervous system metastases.
- The agent is being evaluated in the phase 1/2a ReSPECT-LM trial (NCT05034497) for patients with leptomeningeal metastases and in the phase 1/2 ReSPECT-GBM trial (NCT01906385) for patients with recurrent glioblastoma.
- With the orphan drug designation awarded to rhenium obisbemeda, Plus Therapeutics is eligible for benefits, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees, and 7 years of postapproval marketing exclusivity.
Rhenium (186Re) obisbemeda has been granted an orphan drug designation by the FDA as a potential treatment option for patients with breast cancer and leptomeningeal metastases, according to Plus Therapeutics.1
“Receiving an orphan drug designation from the FDA is important validation of our radiotherapeutic candidate for [patients with breast cancer] with leptomeningeal metastases who currently have no FDA-approved treatment options,” said Marc H. Hedrick, MD, president and CEO of Plus Therapeutics, in a press release. “Leptomeningeal metastasis is a rapidly progressing and fatal complication of several cancers, including breast cancer, and incidence continues to rise. Orphan drug designation status, together with the previously granted fast track designation, underscores the significant and urgent need for new treatment options for leptomeningeal metastases.”
Rhenium obisbemeda is a novel, injectable radiotherapy. The agent works by delivering a highly targeted high dose of radiation to central nervous system (CNS) metastases. Additionally, rhenium-186 has a short half-life, beta energy that can destroy cancerous tissue, and gamma energy for live imaging.
In October 2023, positive data from the dose-escalation portion of ReSPECT-LM was reported, and a fast track designation was granted to rhenium obisbemeda from the FDA.
The phase 1/2a ReSPECT-LM trial (NCT05034497) is evaluating the agent for the treatment of patients with leptomeningeal metastases.2 Cohort 4 has finished enrollment, and the company plans to advance to cohort 5 following a standard safety review.3
According to previously reported data from cohorts 1 to 3 of phase 1, part A of ReSPECT-LM, the average reduction in CNS tumor cell count among the 10 evaluable patients treated with rhenium obisbemeda was 53% at day 28. Based on these findings, the FDA approved further dose-escalation and dose-expansion in cohorts 4 to 7. Further, there were no dose-limiting toxicities (DLTs) seen in cohort 4 at doses up to 44.10 mCi.
In the study, enrollment is open to patients 18 years or older who have documented and confirmed leptomeningeal metastases that are type 1 or 2 of any primary type. Other requirements include having a Karnofsky performance status of at least 60, acceptable liver function, adequate renal function, a serum creatinine level up to 2 times the upper limit of normal, and adequate hematologic status.2 If patients have 2D leptomeningeal metastases, they will be excluded from the study.
Once enrolled, patients are being treated with rhenium obisbemeda as a single 5-cc dose. Between 3 and 6 patients are being treated at each dose level. If the initial 3 patients who are enrolled in each cohort do not experience DLTs, the next cohort, which will receive rhenium obisbemeda at a higher dose, will be open for enrollment.
The primary end points of the study are safety and the incidence of DLTs, and secondary end points consist of overall response rate, duration of response, progression-free survival, and overall survival. Dosing in cohort 5 of the study is planned to be initiated by the end of 2023. After the Society for Neuro-Oncology Annual Meeting in November, Plus Therapeutics expects to release additional data in 2024.1
In addition to this study, rhenium obisbemeda is being evaluated for the treatment of recurrent glioblastoma in the ReSPECT-GBM trial.
“We believe rhenium obisbemeda has the potential to address this unmet need, and we look forward to continued progress of our ReSPECT-LM program,” Hedrick said in the press release.
References
1. Plus Therapeutics granted US FDA orphan drug designation to rhenium (186Re) obisbemeda for the treatment of breast cancer with leptomeningeal metastases. News release. Plus Therapeutics. November 3, 2023. Accessed November 3, 2023. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-granted-us-fda-orphan-drug-designation-rhenium
2. Intraventricular administration of rhenium-186 nanoliposome for leptomeningeal metastases (ReSPECT-LM). ClinicalTrials.gov. Updated August 14, 2023. Accessed November 3, 2023. https://clinicaltrials.gov/study/NCT05034497
3. Plus Therapeutics completes dosing in cohort 4 of ReSPECT-LM phase 1 clinical trial of rhenium (¹⁸⁶Re) obisbemeda in leptomeningeal metastases. News release. Plus Therapeutics. October 10, 2023. Accessed November 3, 2023. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-completes-dosing-cohort-4-respect-lm-phase-1
