Can Radiotherapeutics and Early Detection Offer a Breakthrough for Rare CNS Cancer?

Over the past generation, advances in treating common cancers—breast, lung, melanoma, and gastrointestinal (GI)—have improved outcomes in each.1-4 But one complication among them remains incurable: leptomeningeal metastases (LM), which occur when cancer cells spread from the original cancer to the fluid surrounding the brain and spinal cord.

In many cases, LM shows no symptoms at first; then, patients can experience headaches, double vision, nausea, or confusion, followed by difficulty walking and weakness in the limbs.5 There’s no cure; treatment with radiation and chemotherapy seeks to slow progression, and only 7% of patients live a year after diagnosis.5 Approximately 110,000 people are affected by LM each year in the United States.6

Following a patient’s diagnosis, costs to the health system can vary depending on the underlying cancer. A 2020 study found that costs for patients with LM range from $145,000 to $169,000, as up to half of these patients develop neurological impairments.7 The authors concluded that current treatments “come at a significant expense and deliver limited effectiveness.”7

A company called Plus Therapeutics is focused on tackling both parts of this problem. Scientists are developing a targeted treatment for LM, rhenium (Re186) obisbemeda (Reyobiq), and the company has acquired a diagnostic tool that can quickly find tumor cells that have metastasized to the central nervous system (CNS) for patients.8 Plus Therapeutics had previously announced FDA clearance of its investigational new drug application for treatment of pediatric brain cancer; the therapy is also being studied to treat recurrent glioblastoma.9,10

Plus Therapeutics’ subsidiary, CNSide Diagnostics, LLC, is relaunching the CNSide CSF Assay Platform, which uses quantitative analysis to detect cells in circulating tumor DNA of the cerebrospinal fluid (CSF).8 In September, United Healthcare signed a national coverage agreement with CNSide Diagnostics.8

Marc Hedrick, MD | Image: Plus Therapeutics

The need for treatments for LM stems from the success in treating major cancers, said Marc Hedrick, MD, MBA, president and CEO of Plus Therapeutics, in an interview with The American Journal of Managed Care.

“We’re doing a great job taking care of breast cancer, lung cancer, melanoma; in some cases, they become chronic disease. Patients are not cured, but these patients are living for long periods of time, and their local cancer is controlled.”
Patients may stay on maintenance therapy for their primary cancer for an extended period, Hedrick said. A 2022 study published in Neurotherapeutics reported that between 5% and 20% of long-term cancer survivors were at risk of LM.11 With 18.1 million cancer survivors in the US,12 Hedrick said that means “there are about a million patients in the US [with] advanced cancers [who] are walking around at risk for getting leptomeningeal cancer or metastases into the fluid.”

Novel Mechanism, Known Delivery System
The concept of today’s wave of radiopharmaceuticals is to pinpoint delivery, but Hedrick said Plus Therapeutics has taken this a step further. The basic mechanism of radiation therapy, he said, “is pretty simple; it causes the double-strand DNA breaks that are so whelming that the cell can’t recover.”
What’s new is that “no one has ever taken a nuclear radioisotope and incorporated it into a lipid membrane,” Hedrick said. “That is what allows you to load thousands, if not millions of these radioisotopes in a protected envelope. So, they’re shooting the radiation out 2 to 4 mm, but it protects the metabolism of that drug.”

Plus Therapeutics describes the carrier, a nanoliposome, as being able to carry rhenium and remain at its target for several days before degrading naturally within the body.13 “The key thing is, you can deliver it to the region of interest, and it will stay,” Hedrick said. “We’re not really seeing any meaningful systemic toxicity.”

In addition, Hedrick said, the radioisotope used for LM therapy is rhenium-186, which he said is “ideal” for neurologic indications due to its radiation path length and beta energy.

The therapy’s physical properties are well-suited for shipping, and its delivery method uses a port-and-catheter system, administered under the skin of the skull, that Hedrick said has been around for more than 30 years.

Having a delivery system that is familiar to neurosurgeons is significant, Hedrick said. “If we had to build a device business to get this deployed, the adoption cycle would take forever,” he noted.

Positive Phase 1 Data; More Studies Ongoing
Investigators in the phase 1/2, ReSPECT-LM trial (NCT05034497) presented phase 1 results in August 202514 that showed radiographic and clinical response rates of 76% and 87%, respectively. Patients who were treated lived 9 months, compared with an average survival of 4 months in previously published studies.14

Andrew Brenner, MD, PhD, a professor of medicine in the Division of Hematology and Oncology at UT Health San Antonio MD Anderson Cancer Center in Texas, said these responses showed tolerance of doses across a broad therapeutic range. “Furthermore, the trial gave us exactly what we needed to move into the ongoing dosing optimization trial and then to a potential approval trial,” he said in a news release.14

A new clinical trial to test multidose administration (NCT07098806) began on July 2, 2025, with an estimated completion date of October 2026.15 Hedrick said he anticipates the final dosing schedule will be 4 to 8 times per year.

References
1. Breast cancer facts & stats. National Breast Cancer Foundation. Updated September 29, 2025. Accessed October 5, 2025. https://www.nationalbreastcancer.org/breast-cancer-facts/
2. Howlader N, Forjaz G, Mooradian MJ, et al. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383(7):640-649. doi:10.1056/NEJMoa1916623
3. Long-term metastatic melanoma survival dramatically improves on immunotherapy. Dana-Farber Cancer Institute. September 15, 2024. October 5, 2025. https://www.dana-farber.org/newsroom/news-releases/2024/long-term-metastatic-melanoma-survival-dramatically-improves-on-immunotherapy
4. Ali H, Ishtiaq R, Tedder B, et al. Trends in mortality from gastrointestinal, hepatic, and pancreatic cancers in the United States: a comprehensive analysis (1999–2020). JGH Open. 2024;8(4):e13064. doi:10.1002/jgh3.13064
5. Harstad L, Hess KR, Groves MD. Prognostic factors and outcomes in patients with leptomeningeal melanomatosis. Neuro Oncol. 2008;10(6):1010-1018. doi:10.1215/15228517-2008-062
6. Nayar G, Ejikeme T, Chongsathidkiet P, et al. Leptomeningeal disease: current diagnostic and therapeutic strategies. Oncotarget. 2017;8(42):73312-73328. doi:10.18632/oncotarget.20272
7. Adil SM, Hodges SE, Edwards RM, et al. Health care resource utilization and treatment of leptomeningeal carcinomatosis in the United States. Neurooncol Pract 2020;7(6):636–645. doi:10.1093/nop/npaa041
8. Plus Therapeutics announces national coverage agreement with UnitedHealthcare insurance company for CNSide cerebrospinal fluid assay for metastatic CNS cancer. News release. Plus Therapeutics. September 25, 2025. Accessed October 5, 2025. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-announces-national-coverage-agreement
9. Plus Therapeutics announces FDA clearance of its investigational New Drug Application using Reyobiq for the treatment of childhood brain cancer. News release. Plus Therapeutics. June 25, 2025. Accessed October 5, 2025. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-announces-fda-clearance-its-investigational
10. Plus Therapeutics reports ReSPECT-GBM clinical trial update at the 2024 Congress of Neurological Surgeons Annual Meeting. News release. Plus Therapeutics. October 1, 2024. Accessed October 5, 2025. https://ir.plustherapeutics.com/news-
releases/news-release-details/plus-therapeutics-
reports-respect-gbm-clinical-trial-update-2024
11. Wilcox JA, Li MJ, Boire AA. Leptomeningeal metastases: new opportunities in the modern era. Neurotherapeutics. 2022;19(6):1782-1798. doi:10.1007/s13311-022-01261-4
12. National Cancer Survivors Month. National Cancer Institute. Accessed October 5, 2025. https://cancercontrol.cancer.gov/ocs/about/survivorship-month
13. Our platform. Plus Therapeutics. Accessed October 5, 2025. https://plustherapeutics.com/our-
platform/
14. Plus Therapeutics presents positive ReSPECT-LM clinical trial results of Reyobiq in leptomeningeal metastases. News release. Plus Therapeutics. August 18, 2025. Accessed October 5, 2025. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-presents-positive-respect-lm-clinical-trial
15. Multiple dose intraventricular administration of rhenium-186 nanoliposome for leptomeningeal metastases (CA2024-LM-001). ClinicalTrials.gov. Updated August 1, 2025. Accessed October 5, 2025. https://clinicaltrials.gov/study/NCT07098806