Phase 1 RNL-186 Shows Promise for Leptomeningeal Metastases: Andrew Brenner, MD, PhD

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A new phase 1 trial treating leptomeningeal metastases (LM) in patients with metastatic cancer demonstrated substantial safety and efficacy, prompting a phase 2 trial to further evaluate adequate fractionation dosing schedules.1

The findings were presented at the 2025 San Antonio Breast Cancer Symposium by Andrew Brenner, MD, PhD, a breast and neuro-oncologist specialist and professor of medicine in the Division of Hematology and Oncology at the University of Texas Health Science Center at San Antonio. Patients in the phase 1 trial, ReSPECT-LM (NCT05034497), were given Rhenium-186 NanoLiposome (RNL-186) through an intraventricular catheter. RNL-186 is a radioisotope, and although radioisotopes have been used for decades to treat cancer, their usage has been limited because “radioisotopes don’t have a natural avidity for cancer,” Brenner said in an interview with The American Journal of Managed Care®.

However, what’s unique about this particular therapy is that, unlike radioisotopes used in thyroid cancer, which can be treated with a radioiodine, this therapy uses a BMEDA molecule to help the radioisotopes bind to the liposomes that are absorbed by the cancer cells, Brenner explained.

“The general idea is we have a path length with this particular isotope that allows [us to] treat the spinal fluid and brain surface with high precision and careful attention but spares the deeper, more sensitive areas of the brain and spinal cord,” Brenner said.

Although this therapy can be used to treat a variety of metastatic cancers of the lung, breast, and melanoma, breast cancer is the most common cancer linked to LM. Of the 21 evaluable patients in the trial, 10 (48%) had breast cancer as their primary cancer.2 Although the breast cancer sample size was too small to make a generalizable assumption on the efficacy of RNL-186 on the various subtypes of breast cancer, the abstract concluded that the response rates and survival among patients with breast cancer were also promising. Seven of the 8 patients with breast cancer with circulating tumor cell studies showed partial response, with 1 of 8 showing stable disease symptoms.1

Clinical response with evident decrease in disease symptoms was noted in 3 patients, with 3 patients experiencing stable symptoms through day 112. Radiographic response data were available for 17 patients, of whom 5 experienced partial responses and 8 experienced stable disease through day 112, demonstrating a 76% benefit rate. Clinical response with a decrease in disease symptoms was noted in 2 of the 15 evaluable patients, and 11 showed stable symptoms through day 112.

Cerebrospinal fluid tumor cell enumeration (TCE) assays on the CNSide test were used to measure the reduction in tumor cells from baseline through follow-up. The maximum reduction was seen at day 28. Five of the 7 total patients with a TCE response greater than 80% survived 1 year or longer following treatment with RNL-186.

“We actually had some patients that had even clinical improvement, which is really difficult to come by, because a lot of times, neurological deficits can be permanent once damage occurs, and some of our patients actually had improvement in their neurologic symptoms,” Brenner said. “All that supports the continued development of this for leptomeningeal metastases.”

References

1. Brenner A, Youssef M, Kumthekar P, et al. Rhenium (¹⁸⁶Re) obisbemeda (rhenium nanoliposome, ¹⁸⁶RNL) for the treatment of leptomeningeal metastases: phase 1 dose escalation study results. Abstract presented at: San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, Texas.

2. Leptomeningeal disease: what it is, symptoms & prognosis. Cleveland Clinic. October 14, 2025. Accessed December 17, 2025. https://my.clevelandclinic.org/health/diseases/22737-leptomeningeal-disease