FDA Grants Orphan Drug Designation to Novel Treatment for Leptomeningeal Metastases in Breast Cancer

Plus Therapeutics has announced that the FDA granted orphan drug designation to rhenium (186Re) obisbemeda for the treatment of leptomeningeal metastases in breast cancer.¹

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The novel, injectable radiotherapy is designed to provide a highly targeted, high dose of radiation to metastases in the central nervous system (CNS). Rhenium-186 has a limited half-life, beta energy to destroy cancerous tissue, and gamma energy for live imaging, according to Plus Therapeutics.

“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, Plus Therapeutics, 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. We believe rhenium obisbemeda has the potential to address this unmet need, and we look forward to continued progress of our ReSPECT-LM program.”¹

Rhenium obisbemeda is currently being studied in patients with leptomeningeal metastases in the phase 1/2a ReSPECT-LM (NCT05034497) trial, which has recently completed patient enrollment for cohort 4. Investigators intend to advance to cohort 5 after completing a standard safety review.

Further, data from ReSPECT-LM are anticipated to be provided at the Society for Neuro-Oncology Annual Meeting in November 2023. Rhenium obisbemeda is also being analyzed among patients with recurrent glioma in the phase 1/2 ReSPECT-GBM trial (NCT01906385).

Last month, Plus Therapeutics announced that it had completed dosing in cohort 4 of the study following the release of positive data from the dose escalation portion of ReSPECT-LM and that the FDA granted rhenium obisbemeda with fast track designation.²

Among cohorts 1 to 3 in phase 1 of the trial, part A of ReSPECT-LM data show that evaluable patients administered rhenium obisbemeda (n = 10) experienced an average decrease in CNS tumor cell counts of 53% at day 28. The FDA then approved additional dose escalation and expansion in cohorts 4 to 7. Investigators did not observe dose-limiting toxicities (DLTs) at doses up to 44.10 mCi among cohort 4.

Plus Therapeutics said that it will begin dosing in cohort 5 by the end of 2023, and anticipates releasing additional data in 2024 following the Society for Neuro-Oncology Annual Meeting in November.

Eligibility for enrollment in ReSPECT-LM requires patients to be 18 years of age or older at the time of screening with documented and confirmed leptomeningeal metastases that are type 1 or 2 of any primary type.

Additionally, enrollees should have a Karnofsky performance status of at least 60, acceptable liver function, adequate renal function, serum creatinine level up to twice the upper limit of normal, and adequate hematologic status.³

Exclusion criteria include the presence of 2D leptomeningeal metastases; unresolved adverse effects from prior treatment; obstructive or symptomatic communicating hydrocephalus; and the presence of ventriculoperitoneal or ventriculoatrial shunts without programable valves or contraindications to placement of Ommaya reservoir. Individuals with serious intercurrent illness are also ineligible for enrollment.

Those who have had any dose of radiation to the spinal cord or whole brain radiation therapy are unable to enroll, but administration of non-CNS radiation to the primary tumor is permitted. Administration of systemic chemotherapeutic agents with CNS penetration are not permitted within 14 days or 5 half-lives prior to the study treatment.

Investigators will administer a single 5 cc dose of rhenium obisbemeda, with between 3 and 6 patients treated at each dose level. In the event that DLTs do not occur in the first 3 patients enrolled to each cohort, the subsequent cohort at a higher dose level will open for enrollment.

The primary endpoint of the trial is safety and incidence of DLTs, with secondary end points that include overall response rate, duration of response, progression-free survival, and overall survival.

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