FDA Grants Rhenium Obisbemeda Orphan Drug Status for LM in Lung Cancer

US FDA

• The FDA has granted orphan drug designation (ODD) to rhenium (186Re) obisbemeda for the potential treatment of patients with leptomeningeal metastases (LM) in patients with lung cancer.
• Rhenium obisbemeda is a novel, injectable radiotherapy.
• The agent was just evaluated in the phase 1/2a ReSPECT-LM trial (NCT05034497) for patients with LM, as well as in the in the phase 1/2 ReSPECT-GBM trial (NCT01906385) for patients with recurrent glioblastoma.

The FDA granted rhenium obisbemeda ODD for the treatment of patients with LM in patients with lung cancer.¹

This designation follows the recent completion of the phase 1 ReSPECT-LM trial. This single-dose trial determined the recommended phase 2 dose (RP2D) of rhenium obisbemeda in this patient population.

Now, a phase 2, single-dose expansion trial and a phase 1 multiple-dose trial plan to further evaluate the agent in patients with lung cancer with LM. The company is currently engaging the FDA to define the optimal pivotal trial strategy.

“Receiving orphan drug designation for rhenium (186Re) obisbemeda marks a significant milestone in our efforts to develop a much-needed therapy for lung cancer patients with leptomeningeal metastases,” said Mike Rosol, PhD, Plus Therapeutics chief development officer, in a press release. “These patients currently have limited treatment options, and the growing incidence of LM in lung cancer underscores the urgency for new therapies.”

Microscopic, photorealistic image of lung cancer cells - Generated with Adobe Firefly

Rhenium obisbemeda, a novel, injectable radiotherapy, delivers a highly targeted, high dose of radiation to central nervous system (CNS) metastases. Rhenium-186 has a short half-life, beta energy that works to destroy cancerous tissue, and gamma energy for live imaging.²

In October 2023, positive data from the dose-escalation portion of ReSPECT-LM was announced, showing that in 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 28.³ With this, the FDA approved further dose-escalation and dose-expansion in cohorts 4 to 7. Additionally, no dose-limiting toxicities (DLTs) were seen in cohort 4 at doses up to 44.10 mCi.

Along with the release of these data, the FDA granted the agent fast track designation, followed by an ODD for the treatment of LM and breast cancer in November 2023.²

“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,” said Rosol in the press release.¹

About the ReSPECT-LM Trial

ReSPECT-LM is a phase 1/2a trial assessing the Rhenium obisbemeda for the treatment of patients with LM.Patients aged 18 years or older who have documented and confirmed LM that are type 1 or 2 of any primary type were eligible for enrollment in the study. Patients were also required to 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.⁴

Rhenium obisbemeda was given to patients as a single 5 cc dose, with between 3 and 6 patients 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 consist of safety and the incidence of DLTs. Secondary end points include overall response rate, duration of response, progression-free survival, and overall survival.

Rhenium obisbemeda is also undergoing evaluation in the ReSPECT-GBM trial for the treatment of recurrent glioblastoma.

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. News release. https://tinyurl.com/3e2fxsyw

2. 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 March 6, 2025. https://tinyurl.com/mr6umxn9

3. 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 March 5, 2025. https://tinyurl.com/23ksnzav

4. Intraventricular administration of rhenium-186 nanoliposome for leptomeningeal metastases (ReSPECT-LM). ClinicalTrials.gov. Updated November 26, 2024. Accessed March 5, 2025. https://tinyurl.com/yck64yex