FDA Grants ODD to Rhenium Obisbemeda for Breast Cancer and Leptomeningeal Metastases
Rhenium obisbemeda shows potential to address the unmet need of new treatment options for patients with breast cancer and leptomeningeal metastases and will continue to be evaluated in the ReSPECT-LM program.
- Rhenium (186Re) obisbemeda is a novel, injectable radiotherapy which 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 in the phase 1/2 ReSPECT-GBM trial (NCT01906385) for patients with recurrent gliblastoma.
- With the orphan drug designation (ODD) 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 post-approval marketing exclusivity.
An ODD has been granted by the FDA to rhenium (186Re) obisbemeda as a potential treatment option for patients with breast cancer and leptomeningeal metastases, according to Plus Therapeutics.1
“Receiving 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 chief executive officer 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.”
Breast Cancer Image: © Giovanni Cancemi- stock.adobe.com
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 is evaluating the agent for the treatment of patients with leptomeningeal metastases. Cohort 4 has finished enrollment, and the company plans to advance to cohort 5 following a standard safety review.2
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.3 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 give rhenium obisbemeda at a higher dose level, 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.
“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 a press release.1
REFERENCES
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://tinyurl.com/mr6umxn9
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://tinyurl.com/23ksnzav
Intraventricular administration of rhenium-186 nanoliposome for leptomeningeal metastases (ReSPECT-LM). ClinicalTrials.gov. Updated August 14, 2023. Accessed November 3, 2023. https://tinyurl.com/yck64yex
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