Forty to fifty percent of newly diagnosed DLBCL patients will relapse and another 10% will be refractory to initial therapy. Despite the introduction of new therapies, outcomes for patients with R/R DLBCL remain poor with no improvement in progression free survival (PFS), overall survival (OS) or response rates (ORR). Patients receiving 1 additional line of treatment have an OS of ∼13 months post relapse and for those requiring 3rd line treatment or more, only 10% survive for 12 months. CLR 131 is a novel therapeutic being evaluated in R/R DLBCL. CLR 131 leverages a novel delivery mechanism that takes advantage of a metabolic shift in tumor cells to allow the targeted delivery of I-131 directly into tumour cells.
A multi-center study is being conducted to evaluate the safety and efficacy of CLR 131 in patients with R/R DLBCL. An interim assessment was conducted to determine cohort expansion and continued enrollment of up to 40 additional patients. The criteria for expansion was a minimum 20% of patients experience clinical benefit (CBR) or better. Patients in this assessment received a single 25mCi/m2 30-minute infusion of the targeted radiotherapeutic CLR 131 on day 0. Patients were then followed until disease progression. The primary endpoint is CBR. Secondary endpoints included ORR, PFS and OS.
Six R/R DLBCL patients having received an average of 3 prior lines of therapy received a single infusion of CLR 131. Overall 3/6 patients achieved CBR, 1 patient experienced a complete response (CR) with a total reduction in tumor volume of greater than 99% and continues to be a CR at nearly 8 months post dosing. One patient with cutaneous R/R DLBCL achieved a partial response (PR) with a 56% reduction in total tumor volume and 1 achieved stable disease. The average duration of response was ∼5 months and continues to be monitored. PFS and OS have not been reached at the time of submission.
In this interim evaluation of CLR 131 in R/R DLBCL patients, significant and durable responses were exhibited, including a 33% ORR, 15% CR and 50% CBR. Patients experienced durable responses (assessment continues). Larger, prospective trials are needed to elucidate optimal patient and dosing schedule of CLR 131 in these patients.
Clinical trial identification
Legal entity responsible for the study
Cellectar Biosciences, Inc.
National Institutes of Health, National Cancer Institute.
J. Longcor: Full / Part-time employment: Cellectar Biosciences, Inc. K. Oliver: Full / Part-time employment: Cellectar Biosciences Inc. J. Friend: Full / Part-time employment, Formerly: Cellectar Biosciences Inc. All other authors have declared no conflicts of interest.