FDA Grants Orphan Drug Designation to Rhenium (186Re) Obisbemeda for Leptomeningeal Metastases in Lung Cancer

The FDA has granted orphan drug designation to the investigational radiotherapeutic rhenium (186Re) obisbemeda as a potential therapeutic option for leptomeningeal metastases in patients with lung cancer.1

Rhenium (186Re) obisbemeda is formulated to deliver highly targeted, high-dose radiation directly to central nervous system (CNS) tumors with the goal of optimizing safety and efficacy via a more potent and localized radiation dose compared with currently available treatments.

“Receiving orphan drug designation for rhenium (186Re) obisbemeda marks a significant milestone in our efforts to develop a much-needed therapy for [patients with] lung cancer with leptomeningeal metastases,” Mike Rosol, PhD,, chief development officer of Plus Therapeutics, stated in a news release. “These patients currently have limited treatment options, and the growing incidence of leptomeningeal metastases in lung cancer underscores the urgency for new therapies. This designation, in combination with our previously granted fast track designation, strengthens our pathway toward delivering an innovative, targeted radiotherapeutic solution for this highly underserved patient population.”

The phase 1 ReSPECT-LM clinical trial (NCT05034497) evaluated rhenium (186Re) obisbemeda in patients with LM and established the recommended phase 2 dose (RP2D). After enrollment was completed for cohort 6, which evaluated that agent at a dose of 75.0 mCi, the cohort 4 dose of 44.1 mCi was determined to be the RP2D; no dose-limiting toxicities were observed at this dose level.2

One patient treated at the cohort 4 dose achieved a complete response, as evidenced by the eradication of tumor cells in the cerebrospinal fluid—a key therapeutic end point.

The company is advancing a phase 2 single-dose expansion trial and a phase 1 multiple-dose trial to further assess the agent’s safety and therapeutic potential.1 Additionally, ongoing discussions with the FDA aim to define the optimal design for a pivotal registration trial.

Rhenium (186Re) obisbemeda is also being evaluated for the treatment of patients with recurrent glioblastoma in the phase 1/2 ReSPECT-GBM trial (NCT01906385).

ReSPECT-LM Patient Enrollment Criteria

The study evaluated rhenium (186Re) obisbemeda in patients at least 18 years of age with documented leptomeningeal metastases meeting type 1 or 2 criteria per the EANO-ESMO Clinical Practice Guidelines.3 Patients needed to have a Karnofsky performance status of at least 60 and adequate liver, kidney, and hematologic function.

Key exclusion criteria included unresolved adverse effects (AEs) greater than grade 1 from prior antineoplastic therapy; obstructive or symptomatic communicating hydrocephalus; contraindications to Ommaya reservoir placement; and significant comorbidities such as progressive systemic disease, severe cardiac conditions, uncontrolled infections, or severe nonhematologic organ toxicity at grade 3 or higher. Patients who received prior spinal cord or whole-brain radiation therapy were also excluded; however, those given prior non-CNS radiation for a primary tumor were eligible.

Additionally, the study excluded patients who received systemic chemotherapeutic agents with CNS penetration within 14 days or five half-lives of treatment; nitrosoureas or mitomycin C within 42 days; metronomic chemotherapy within 14 days; or other cytotoxic chemotherapy within 28 days.

Enrolled patients received a single dose of rhenium (186Re) obisbemeda during the dose-escalation study. Three to 6 patients were treated at each dose level, and if no DLTs were observed in the first 3 patients treated in a given cohort, enrollment was allowed to begin in the next cohort evaluating a higher dose level.

The primary outcomes included the incidence and severity of AEs and serious AEs, which were graded according to the CTCAE 5.0 criteria; and the incidences of DLTs to determine the maximum tolerated dose.

Secondary end points included overall response rate, duration of response, progression-free survival, and overall survival.

References

1. Plus Therapeutics granted U.S. FDA orphan drug designation for Rhenium (186Re) Obisbemeda for the treatment of leptomeningeal metastases in patients with lung cancer. Plus Therapeutics. March 6, 2025. Accessed March 7, 2025. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-granted-us-fda-orphan-drug-designation-0
2. Plus Therapeutics advances lead drug Rhenium (186Re) Obisbemeda for patients with leptomeningeal metastases. Plus Therapeutics. February 26, 2025. Accessed March 7, 2025. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-advances-lead-drug-rhenium-186re-obisbemeda
3. Intraventricular administration of Rhenium-186 NanoLiposome for leptomeningeal metastases (ReSPECT-LM). Clinicaltrials.gov. Updated November 24, 2024. Accessed March 7, 2025. https://clinicaltrials.gov/study/NCT05034497