186Re Obisbemeda Earns FDA ODD in Leptomeningeal Metastatic Breast Cancer
Investigators are assessing rhenium obisbemeda as a treatment for breast cancer harboring leptomeningeal metastases as part of the phase 1/2a ReSPECT-LM trial.
Investigators are currently assessing 186Re obisbemeda among patients with leptomeningeal metastases in the phase 1/2a ReSPECT-LM trial (NCT05034497).
The FDA has granted orphan drug designation to rhenium (186Re) obisbemeda as a treatment for patients with breast cancer harboring leptomeningeal metastases, according to a press release from Plus Therapeutics, Inc.1
Developers designed 186Re obisbemeda to administer highly targeted radiation at high volumes to central nervous system (CNS) tumors. It is believed to be an ideal radioisotope for managing this type of malignancy based on characteristics including its short half-life, beta energy for attacking cancer in tissues, and gamma energy for enabling 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 at Plus Therapeutics, said in the press release.1 “[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].”
Investigators are currently assessing 186Re obisbemeda among patients with leptomeningeal metastases in the phase 1/2a ReSPECT-LM trial (NCT05034497). According to previously announced data, 10 patients included in part A of the trial received the maximum absorbed dose of 85 Gy and a maximum of 26.4 mCi with respect to radiation activity.2 Investigators observed no dose-limiting toxiities and reported that cerebrospinal fluid tumor cell counts were reduced by an average of 53% at 28 days following treatment. Moreover, the median overall survival (OS) was 10 months among half (n = 5/10) of the patients who were alive after receiving treatment in part A.
These findings were presented at the Society for Neuro Oncology (SNO)/American Society of Clinical Oncology (ASCO) CNS Cancer Conference in August 2023. Investigators will present updated results from the trial at 2023 SNO Annual Meeting.
“The phase 1/part A data in the ReSPECT-LM clinical trial is encouraging,” Norman LaFrance MD, chief medical officer at Plus Therapeutics, said in a press release at the time these data were published.2 “In phase 1/part B, we plan to dose escalate to the maximum tolerated single dose while simultaneously collaborating with the FDA to implement multiple dosing into the trial.”
In the dose escalation portion of the multi-center ReSPECT-LM trial, patients received a single 5cc dose of 186Re obisbemeda via Ommaya reservoir. Investigators based their study design on a modified Fibonacci dose escalation scheme.
The trial’s primary end points are adverse effects (AEs) and serious AEs as well as the incidence of dose-limiting toxicities. Secondary end points include overall response rate, duration of response, progression-free survival, and OS.
Patients 18 years and older with current European Association of Neuro-Oncology (EURO)-European Society for Medical Oncology (ESMO) Clinical Practice Type 1 and 2 leptomeningeal metastases of any primary type are eligible for enrollment on the trial. Additional eligibility criteria include a Karnofsky performance status of 60 to 100 and adequate liver and hematologic function.
Those with obstructive or symptomatic communicating hydrocephalus, or ventriculo-peritoneal or ventriculo-atrial shunts that lack programable valves or contraindications to placement of Ommaya reservoir are unable to enroll on the trial. Patients are also unsuitable for enrollment if they have significant coagulation abnormalities including inherited bleeding diathesis or acquired coagulopathy with unacceptable risks of bleeding.
References
- Plus Therapeutics granted U.S. 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 6, 2023. https://bit.ly/3sleNwq
- Plus Therapeutics initiates part B of ReSPECT-LM phase 1/2a trial for leptomeningeal metastases. News release. Plus Therapeutics. September 5, 2023. Accessed November 6, 2023. https://bit.ly/47is73n
