Abstract PD13-04: Rhenium (186Re) obisbemeda (rhenium nanoliposome,186RNL) for the treatment of leptomeningeal metastases (LM): Phase 1 dose escalation study results

Abstract Background: Leptomeningeal metastases (LM) is a devastating systemic cancer complication most often seen with breast, lung, and melanoma, with limited treatment options and poor survival. Rhenium (186Re) Obisbemeda (ReyobiqTM) provides the combination of effective therapeutic beta radiation, simultaneous gamma decay for imaging, and ∼90-hour physical half-life for optimal radiation delivery. A summary of the completed Phase 1 dose escalation study, with an emphasis on those patients with breast cancer primaries, will be presented. Methods: ReSPECT-LM was a Phase 1 dose escalation study for patients with LM from any primary cancer. Adult patients were given a single dose of 186RNL via intraventricular catheter (Ommaya reservoir) in an outpatient setting to determine the maximum tolerated/feasible dose (MTD/MFD), safety, tolerability, and response. Seven administered dose cohorts in a 3+3 design, from 6.6 mCi to 109.96 mCi, were planned. Results: A total of 29 subjects received 6.6, 13.2, 26.4, 44.10, 66.14, or 75 mCi of Reyobiq (cohorts 1-6, respectively). Thirteen of the 29 treated subjects had breast cancer as their primary cancer (45%). Twenty-one subjects were evaluable per protocol (completed Day 28 safety follow up). Ten of the evaluable patients (48%) had primary breast cancer. Five were triple negative (ER negative/PR negative/HER2 negative); three were ER positive/HER2 negative; and two were HER2 positive. Including all evaluable patients, no dose limiting toxicity (DLT) was observed in cohorts 1-4, with 1 DLT of grade 4 cytopenia in each of cohorts 5 and 6. Following the cohort 6 safety review, enrollment was concluded, and the recommended phase 2 dose was determined to be 44.10 mCi. The majority of adverse events across the trial were Grade 1 and 2. There were no serious adverse events reported in the 44.10 mCi dose cohort 4 (n=6). A dose-dependent increase in the absorbed dose to the cranial and spinal subarachnoid space was observed, reaching a mean of 272 Gy in cohort 6. Radiographic response data was available for nine breast cancer patients, with two (22%) showing response based on investigator assessment. An additional four patients showed stable disease through day 112 for a Clinical Benefit Rate (CR+PR+SD) of 67%. Additionally, a clinical response with evident decrease in disease symptoms was noted in three of ten evaluable patients (30%), with three patients (30%) showing stable symptoms through day 112. Radiographic response data available for 17 patients (all primary cancers included) showed five partial responses and eight stable disease through day 112 (76% benefit rate). Additionally, a clinical response with decrease in disease symptoms was noted in two of 15 evaluable patients (13%), and 11 showing stable symptoms through day 112 (clinical benefit rate of 87%). CSF tumor cell enumeration (TCE) assays (CNSide test) were performed with a maximum reduction over baseline of 100% seen at Day 28. Seven of eight breast cancer patients (87.5%) with CTC studies showed partial response, with one of eight stable (12.5%). Five of seven total patients (any primary cancer) with a TCE response >80% survived ≥ 1 year following treatment with Reyobiq. Across cohorts 1-4 (20 patients) median overall survival was nine months, comparing favorably with literature reported survival of ∼4 months. Conclusion: Reyobiq shows excellent safety and promising activity for LM. A single dose for patients with LM was well-tolerated up to the RP2D of 44.10 mCi, with high absorbed doses to the treatment area, acceptable organ doses, and encouraging response and reductions in tumor cell count. Within the breast cancer patients, response rate and survival were also promising. Based on these data, a multiple dose administration dose optimization study has been initiated and is currently enrolling. Citation Format: A. Brenner, M. Youssef, P. Kumthekar, M. Schulder, J. Floyd, A. Bao, W. Phillips, P. Vroman, J. Michalek, M. Moore, M. Rosol, M. Hedrick. Rhenium (186Re) obisbemeda (rhenium nanoliposome,186RNL) for the treatment of leptomeningeal metastases (LM): Phase 1 dose escalation study results [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD13-04.