CLR 131 Induces Encouraging Responses in Relapsed/Refractory LPL and WM

CLR 131 induced an objective response rate (ORR) of 100% as treatment of patients with relapsed/refractory lymphoplasmacytic lymphoma (LPL) and Waldenström’s macroglobulinemia in the ongoing phase 2 CLOVER-1 study, announced Cellectar Biosciences, Inc.

The initial results from this ongoing study will be presented in a poster during the upcoming American Association of Cancer Research's Advances in Malignant Lymphoma meeting, which is being held virtually August 17 to 19, 2020.

CLOVER-1, an open-label, multicenter trial, is being conducted across 10 leading cancer centers in the United States and is enrolling patients with relapsed/refractory B-cell hematologic malignancies. The malignancies being studied in this trial include multiple myeloma, LPL, WM, marginal zone lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. The study is expected to enroll up to 80 patients.

The primary end point of the study is clinical benefit response, defined by the proportion of patients with multiple myeloma following CLR 131 infusion with stringent complete response (CR), CR, very good partial response (PR), PR, and stable disease (SD) per the International Myeloma Working Group criteria, or the proportion of patients with lymphomas following CLR 131 infusion with a CR, PR, or SD per the Lugano classification CT-based response criteria, the International Waldenström’s Macroglobulinemia Society criteria, or the International Chronic Lymphocytic Leukemia criteria.

Secondary end points of this trial also included overall response rate, progression-free survival, median overall survival, and other efficacy markers.

In this trial, patients are treated with 3 different dose levels, which include <60 mCi in a single cycle, >60mCi in a single cycle, and >60 mCi in a multi-cycle, total body dose.

Part A of the study, which is a dose-exploration portion, has been completed in patients with relapsed/refractory B-cell malignancies. Part B, the expansion cohort, is now enrolling patients with relapsed/refractory multiple myeloma, LPL, and WM. This portion of the study will evaluate the 2-cycle dosing of CLR 131. Cycle 2 will be given 8-weeks post-initial infusion, and additional cycles can be considered following an additional 8-week period.

Part A of the CLOVER-1 met both its primary and secondary end points, which were announced in February 2020.

Among 80 patients treated with CLR 131, the ORR was 34.5% over all therapeutic doses in patients with myeloma and was 42% among patients with non-Hodgkin lymphoma. These data also indicated that the ORR among patients with LPL and WM was 100%.

Tumor reductions were observed in 76.7% of patients with myeloma, which may indicate a potential to improve existing responses in these patient populations.

In terms of safety, cytopenia was the most commonly observed adverse event (AE) in patients with myeloma. The most common grade ≥3 AEs were thrombocytopenia (65%), neutropenia (41%), leukopenia (30%), anemia (24%), and lymphopenia (35%). There were no cases of neurotoxicity, cardiotoxicity, infusion site reaction, peripheral neuropathy, allergic reaction, cytokine release syndrome, keratopathy, renal toxicities, or changes in liver enzymes.

Among patients with relapsed/refractory non-Hodgkin lymphoma, the safety profile was the same, except these patients experienced fewer cytopenias compared with patients with multiple myeloma.

The agent also induced a 30% response rate among patients with diffuse large B-cell lymphoma, and 1 patient had a CR, which was ongoing at the data cutoff. A 33% ORR was observed in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, and marginal zone lymphoma. The best response among the 2 patients with mantle cell lymphoma was stable disease.

To be included in the study, patients were required to have an ECOG performance status of 0 to 2, a life expectancy of at least 6 months, and have adequate lab values. Patients with myeloma were required to have progressive disease and at least 2 prior lines of therapy, 1 of which must have been an FDA-approved proteasome inhibitor. Patients who had previous anti-cancer therapy within 2 weeks of initial CLR 131 infusion and those who had prior radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2 weeks of eligibility-defining bone marrow biopsy were ineligible for the study. Patients were also excluded from the study due to certain toxicities and commodities that may have interfered with treatment.

_Reference

_{1. Cellectar biosciences announces poster presentation of clinical data at the American association of cancer research (AACR) annual meeting. July 21, 2020. Accessed July 21, 2020. https://bit.ly/39hoJsQ}

_{2. Cellectar Biosciences announces clr 131 achieves primary efficacy endpoints from its phase 2 clover-1 study in relapsed/refractory b-cell lymphomas and completion of the phase 1 relapsed/refractory multiple myeloma dose escalation study. News Release. February 19, 2020. Accessed July 21, 2020. https://bit.ly/2V4OaZD}