Key points:
- Rhenium(186Re) obisbemeda is a novel injectable radiation therapy that delivers highly targeted, high-dose radiation to central nervous system metastases.
- The agent is being evaluated in the Phase 1/2a ReSPECT-LM trial (NCT05034497) in patients with leptomeningeal metastases and in the Phase 1/2 ReSPECT-GBM trial (NCT01906385) in patients with recurrent glioblastoma.
- With rhenium obisbemeda being granted orphan drug designation, Plus Therapeutics is eligible to receive benefits including assistance during the drug development process, tax credits for clinical expenses, a waiver of certain FDA fees, and seven years of marketing exclusivity following approval. .
rhenium(186According to Plus Therapeutics, Re)obisbemeda has been granted orphan drug designation by the FDA as a potential treatment option for patients with breast cancer and leptomeningeal metastases.1
Marc H. Hedrick, M.D., President and Chief Executive Officer of Plus, said: “Receiving FDA Orphan Drug Designation is an important validation of our radiation therapy candidate for leptomeningeal metastases in breast cancer patients for whom there are currently no FDA-approved treatments. Treatment Options.” Treatment, in a press release. “Leptomeningeal metastases are a rapidly progressive and fatal complication of multiple cancers, including breast cancer, and the incidence continues to increase.” Orphan drug designation status, coupled with the previously granted Fast Track designation, underscores the need for leptomeningeal metastases to There is a significant and urgent need for new treatment options for meningeal metastases. “
Rhenium obisbemeda is a new type of injectable radiation therapy. The drug works by delivering highly targeted, high-dose radiation to central nervous system (CNS) metastases. In addition, rhenium-186 has a short half-life, beta energy can destroy cancer tissue, and gamma energy can be used for real-time imaging.
Images of breast cancer | Image source: Giovanni Cancemi – stock.adobe.com
In October 2023, positive data from the dose escalation portion of ReSPECT-LM were reported, and the FDA granted fast track designation to rhenium obisbemeda.
The drug is being evaluated in the Phase 1/2a ReSPECT-LM trial (NCT05034497) in patients with leptomeningeal metastases.2 Registration for Group 4 has been completed and the company plans to move to Group 5 after a standard security review.3
Based on previously reported data from ReSPECT-LM Part A Phase 1 Cohorts 1 to 3, among 10 evaluable patients treated with rhenium obisbemeda, there was an average reduction in central nervous system tumor cell counts of 53% at day 28. Based on these findings, the FDA approved further dose escalations and dose expansions in Cohorts 4 through 7. Additionally, no dose-limiting toxicities (DLTs) were observed in Cohort 4 at doses up to 44.10 mCi.
In this study, patients aged 18 years or older with documented and confirmed leptomeningeal metastases of any primary type, type 1 or type 2, were recruited. Other requirements include a Karnofsky performance status of at least 60, acceptable liver function, adequate renal function, serum creatinine level up to 2 times the upper limit of normal, and adequate hematologic status.2 Patients were excluded from the study if they had 2D leptomeningeal metastases.
Once enrolled, patients will receive a single 5 cc dose of rhenium obisbemeda. Three to six patients are being treated at each dose level. If the first 3 patients enrolled in each cohort do not experience a DLT, enrollment will open for the next cohort that will receive a higher dose of rhenium obisbemeda.
The primary endpoints of the study were safety and DLT incidence, and secondary endpoints included overall response rate, duration of response, progression-free survival, and overall survival. Dosing in Arm 5 of the study is scheduled to begin in late 2023. Plus Therapeutics expects to release additional data in 2024 following the Society for Neuro-Oncology Annual Meeting in November.1
In addition to this study, the ReSPECT-GBM trial is evaluating rhenium obisbemeda in recurrent glioblastoma.
“We believe rhenium obisbemeda has the potential to address this unmet need, and we look forward to continued progress on the ReSPECT-LM project,” Hedrick said in the release.
refer to
1. Plus Therapeutics granted U.S. FDA orphan drug designation to rhenium (186Re) obisbemeda for the treatment of leptomeningeal metastases of breast cancer. Press Releases. Plus therapy. November 3, 2023. Accessed 3 November 2023. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-granted-us-fda-orphan-drug-designation-rhenium
2. Intraventricular injection of rhenium-186 nanoliposomes for the treatment of leptomeningeal metastases (ReSPECT-LM). clinicaltrials.gov. Updated on August 14, 2023. Accessed November 3, 2023. https://clinicaltrials.gov/study/NCT05034497
3. Plus Therapeutics completed the administration of rhenium(186Re) obisbemeda in leptomeningeal metastases in Cohort 4 of the ReSPECT-LM Phase 1 clinical trial. Press Releases. Plus therapy. October 10, 2023. Accessed 3 November 2023. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-completes-dosing-cohort-4-respect-lm-phase-1