Rhenium (Re186) Obisbemeda Shows Initial Safety, Clinical Benefit in Leptomeningeal Metastases

Leptomeningeal Metastases |

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Single-dose rhenium (Re186) obisbemeda (Reyobiq; 186RNL) was well tolerated and has demonstrated early clinical benefit in patients with leptomeningeal metastases, according to data from the phase 1 dose-escalation ReSPECT-LM trial (NCT05034497).1,2

Data presented in a poster at the 2025 Nuclear Medicine and Neurooncology Conference demonstrated that, as of the data cutoff, 31% of patients (n = 17) demonstrated a radiographic response based on investigator assessment. An additional 8 patients demonstrated stable disease through day 112 for a clinical benefit rate (CBR) of 76%. Moreover, 14% of evaluable patients (n = 15) demonstrated a clinical response with an evident decrease in disease symptoms. Eleven patients demonstrated stable symptoms through day 112, resulting in a CBR of 87%.

Dose-limiting toxicities (DLT) of grade 4 thrombocytopenia (n = 1) and grade 4 lymphocytopenia and neutropenia (n = 1) were observed at the 66.14 mCi dose (cohort 5) and 75 mCi dose (cohort 6), respectively. One death was reported in cohort 6; this was deemed likely unrelated to treatment with 186RNL.2 In the overall study population (n = 21), all patients experienced serious adverse effects (SAEs), which comprised 9% of all AEs observed in the study. Notably, the 44.1 mCi dose (cohort 4) was established as the recommended phase 2 dose (RP2D).

“These newly presented data shows safety, clinical benefit, and data supporting the underlying mechanism of action for [186RNL] in patients with leptomeningeal metastases,” Marc H. Hendrick, MD, Plus Therapeutics President and CEO, stated in a news release.1 “Furthermore, multiple doses of [186RNL] were administered under compassionate use, mirroring how [186RNL] may one day be used post approval and can contribute to long-term survival in leptomeningeal metastases.”

ReSPECT-LM Design and Patient Characteristics

186RNL is a novel injectable radiotherapy formulated to deliver targeted high-dose radiation in central nervous system tumors.

The multicenter, sequential cohort, open-label, dose-escalation study evaluated the safety profile of 186RNL as a single-dose treatment via an intraventricular route in adult patients with leptomeningeal metastases from a primary cancer, including lung and breast cancer.2 Eligible patients were at least 18 years of age; had evidence of leptomeningeal metastases according to EANO-ESMO Clinical Practice Guidelines Type 1 and 2, excepting 2D; had acceptable liver function and hematologic statuses; and had a Karnofsky performance status of 60 to 100.3

The study included 7 cohorts, 6 of which have been completed, to determine the maximum tolerated dose (MTD) of 186RNL.2 These included cohort 1 (6.6 mCi), cohort 2 (13.2 mCi), cohort 3 (26.4 mCi), cohort 4 (44.10 mCi), cohort 5 (66.14 mCi), cohort 6 (75.00 mCi), and cohort 7 (dose to be determined).

The primary end point was the MTD and maximum feasible dose in the 7 cohorts. Exploratory end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).3

In the intention-to-treat population (n = 29), ages ranging from 29 to 76 years and the majority of patients were female (66%). Primary tumors included breast (45%), lung (24%), and other (31%).2

Additional Safety and Early Efficacy Data

Regarding safety, any-grade treatment-related AEs (TRAEs) were observed in all patients (n = 21), 33% of which were grade 3 or higher. The most common TRAEs occurring in at least 10% of patients included headache (any grade, 48%; grade ≥3, 0%), lymphopenia (38%; 19%), vomiting (38%; 0%), thrombocytopenia (33%; 19%), nausea (29%; 0%), hypoalbuminemia (24%; 0%), leukopenia (19%; 10%), increased levels of alanine aminotransferase, anemia, dizziness, eye pain, fatigue, gait disturbance, hyperglycemia, and muscle weakness (10%; 0% each).

Notably, a dose-dependent increase in the absorbed dose of 186RNL in the cranial and spinal subarachnoid space was observed. Clinically significant doses were reported in cohort 1 and reached an average absorbed dose to the cranial subarachnoid space of 235 Gy in cohort 5. However, the average absorbed dose was not clinically significant in the blood, liver, and spleen, excepting bone marrow–absorbed doses approaching general toxicity limits of 2 to 3 Gy in cohort 5.

Based on the analysis of cerebrospinal fluid (CSF) tumor cells before and after administration of 186RNL, patients achieved complete (n = 1/15) and partial (n = 12/15) responses following treatment.2 Additionally, 1 patient experienced disease progression, and 1 had stable disease. At the time of analysis (May 5, 2025), 5 of 7 patients who achieved a more than 80% reduction in circulating tumor cells (CTC) survived at least 1 year following original treatment. Three of these 5 patients were retreated under compassionate use.

Several long-term survivors were reported as of May 2025, including patients who received multiple doses under compassionate use. At screening, patients in cohort 5 were considered to experience the most disease burden, which may have contributed to shorter OS, study authors noted. The median OS in patients from cohorts 1 to 4 (n = 16) was 9 months (95% CI, 1-not applicable).

References

1. Plus Therapeutics’ Reyobiq shows clinical benefit and safety in the ReSPECT-LM clinical trial for patients with leptomeningeal metastases (LM). News release. Plus Therapeutics. May 14, 2025. Accessed May 14, 2025. https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-reyobiqtm-shows-clinical-benefit-and-safety
2. Brenner A, Youssef M, D’Amico R, et al. Rhenium obisbemeda (Reyobiq) in leptomeningeal metastases. Presented at: 2025 Nuclear Medicine and Neurooncology Conference; May 9-10, 2025; Vienna, Austria.
3. Intraventricular administration of rhenium-186 nanoliposome for leptomeningeal metastases (ReSPECT-LM). ClinicalTrials.gov. Updated March 26, 2025. Accessed May 14, 2025. https://clinicaltrials.gov/study/NCT05034497