FDA Awards Orphan Drug Designation to Rhenium Obisbemeda in Breast Cancer With Leptomeningeal Metastases

The FDA has granted an orphan drug designation to rhenium (¹⁸⁶Re) obisbemeda as a potential therapeutic option for patients with breast cancer and leptomeningeal metastases, according to an announcement from Plus Therapeutics.¹

Rhenium obisbemeda is a novel, injectable radiotherapy designed to deliver a highly targeted, high dose of radiation to central nervous system (CNS) metastases. Rhenium-186 has a short half-life, beta energy to destroy cancerous tissue, and gamma energy for live imaging.

“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,” Marc H. Hedrick, MD, president and chief executive officer of Plus Therapeutics, stated in the 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.”

The evaluation of this agent in patients with leptomeningeal metastases is currently underway in the phase 1/2a ReSPECT-LM trial (NCT05034497), and cohort 4 has finished enrollment. Plus Therapeutics plans to advance to cohort 5 following a standard safety review. Additionally, updates from the ReSPECT-LM trial are expected to be read out at the Society for Neuro-Oncology Annual Meeting in November 2023. The agent is also being evaluated in patients with recurrent glioma in the phase 1/2 ReSPECT-GBM trial (NCT01906385).

In October 2023, Plus Therapeutics announced that following positive data from the dose escalation portion of ReSPECT-LM and fast track designation from the FDA, investigators had completed dosing in cohort 4 of the study.²

Prior data from cohorts 1 to 3 of phase 1, part A of ReSPECT-LM showed that in evaluable patients treated with rhenium obisbemeda (n = 10), the agent elicited an average reduction in CNS tumor cell counts of 53% at day 28. The FDA has approved further dose escalation and expansion in cohorts 4 to 7. In cohort 4, no dose-limiting toxicities (DLTs) were observed at doses up to 44.10 mCi.

Plus Therapeutics aims to commence dosing in cohort 5 by the end of 2023, and following the Society for Neuro-Oncology Annual Meeting in November, the Company expects to release additional data in 2024.

Patients 18 years or older at the time of screening with documented and confirmed leptomeningeal metastases that are type 1 or 2 of any primary type are eligible for enrollment in ReSPECT-LM. Notably, patients with 2D leptomeningeal metastases are excluded. Patients should have 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

Exclusion criteria include unresolved adverse effects from previous treatments; obstructive or symptomatic communicating hydrocephalus; and presence of ventriculoperitoneal or ventriculoatrial shunts without programable valves or contraindications to placement of Ommaya reservoir. Furthermore, patients with serious intercurrent illness are not eligible. Patients who have had any dose of radiation to the spinal cord or whole brain radiation therapy cannot enroll; however, non-CNS radiation to the primary tumor is permitted. Systemic chemotherapeutic agents with CNS penetration are not allowed within 14 days or 5 half-lives prior to the study treatment.

Enrolled patients are receiving a single 5 cc dose of rhenium obisbemeda, and between 3 and 6 patients are being treated at each dose level. If DLTs do not occur in the initial 3 patients enrolled to each cohort, the next cohort at a higher dose level is allowed to open for enrollment.

Safety and the incidence of DLTs are the trial’s primary end points. Secondary end points include overall response rate, duration of response, progression-free survival, and overall survival.

“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 added.¹

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. 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
3. 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