277O - The ReSPECT-GBM™ phase I/IIa trial of rhenium-186 nanoliposome (186RNL) in recurrent glioma via convection enhanced delivery (CED) and planned phase IIb trial

Background

A phase I/IIa dose escalation trial was initiated to determine the safety and recommended phase II dose (RP2D) of ¹⁸⁶RNL in patients with recurrent glioma. ¹⁸⁶RNL is a source of high energy beta and gamma particles. We report the safety, feasibility, overall survival (OS), RP2D and proposed phase IIb clinical plan.

Methods

All recurrent glioma patients had computerized treatment planning and up to 4 intracranial catheter(s) placed. Each patient received a single administration of 186RNL by CED. Whole body planar and SPECT/CT imaging on days 1-8 following treatment assessed dosimetry and radiation distribution. Patients were followed for safety, sufficiency of radiation delivery and OS.

Results

Twenty-one patients across 6 dose cohorts received 1.0-22.3mCi in 0.6-8.8mL. Mean tumor volume was 8.3mL. Patients had a mean of 1.7 recurrences and poor prognostic factors. Mean absorbed radiation dose to the tumor (MARDT) was 271Gy with negligible systemic exposure. There were no dose limiting toxicities and the overall safety profile was favorable. Patients were stratified by MARDT. Those receiving >100Gy MARDT (n=12) had a median and mean OS of 129.7 (95% CI 35 to 169.1) and 106.4±19.7 weeks respectively with 4 patients alive. Patients receiving ≤100Gy MARDT (n=9) had a median and mean OS of 22.3 (95% CI 6.4 to 45.3) and 24.6±4.8 weeks respectively, none are alive. Kaplan Meier analysis of patients receiving MARDT >100Gy vs. those with ≤100Gy showed a statistically significant difference in OS (p<0.001). Table: 277O

Conclusions

A single administration of ¹⁸⁶RNL by CED in recurrent glioma patients with poor prognosis is feasible, safe, and potentially effective in increasing OS when >100Gy radiation is delivered to the tumor. A RP2D of 22.3mCi/8.8mL was selected for patients with tumors of up to 15mL in the PIIb trial planned for 2022. The PIIb trial design and comparative survival data (synthetic control arm) will also be presented.

Clinical trial identification

NCT011906385.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

NIH/National Cancer Institute, Plus Therapeutics.

Disclosure

A.J. Brenner: Financial Interests, Personal, Ownership Interest: NanoTx; Financial Interests, Personal and Institutional, Research Grant: NIH/NCI; Financial Interests, Personal, Advisory Role: Plus Therapeutics. W.T. Phillips, A. Bao: Financial Interests, Personal, Ownership Interest: NanoTX; Financial Interests, Personal, Advisory Role: Plus Therapeutics. M.H.H. Hedrick: Financial Interests, Personal and Institutional, Member of the Board of Directors: Plus Therapeutics. N. LaFrance: Financial Interests, Personal, Full or part-time Employment: Plus. All other authors have declared no conflicts of interest.