The first-in-class radioiodinated phospholipid drug conjugate CLR 131 elicited a clinically meaningful overall response rate of 40% in patients with triple-class refractory multiple myeloma who received a total administered dose of 60 mCi or greater.
The first-in-class radioiodinated phospholipid drug conjugate CLR 131 elicited a clinically meaningful overall response rate (ORR) of 40% in patients with triple-class refractory multiple myeloma who received a total administered dose of 60 mCi or greater, according to results from the phase 2 CLOVER-1 trial (NCT02952508).1
The encouraging response rate was observed in 6 patients who were triple-class refractory and were enrolled to part A of the trial, which had a total of 15 patients. Additional patients are being enrolled to part B from March 2020 through May 2020; all patients enrolled in part B must be triple-class refractory, meaning that they are refractory to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.
The additional 6 participants were considered to be heavily pretreated, having received an average of 9 previous multidrug regimens, according to Cellectar Biosciences, Inc. Half of the 6 patients were given a total dose of greater than 60 mCi, while the other half were given less than 60 mCi. Patients who received the higher dose of the agent experienced stronger responses.
“We remain encouraged by consistency of CLR 131’s efficacy and tolerability data in these extremely challenging to treat [patients with] triple-class refractory multiple myeloma,” John Friend, MD, chief medical officer of Cellectar Biosciences, stated in a press release. “A 40% ORR is a clinically meaningful outcome. For reference purposes, 2 recently approved drugs received a 25% and 31% ORR in [patients with] triple-class refractory [disease]. We look forward to the further development of CLR 131, a first-in-class phospholipid radio conjugate that may provide a significant benefit to patients and treatment alternative for clinicians.”
CLR 131 exploits malignant cells’ selective uptake and retention of phospholipid ethers. Because the membrane compound is unique to the malignant cells, the therapy can be precisely targeted to cancer cells with minimal off-target effects.
In the open-label phase 2 trial, investigators set out to identify the safety and efficacy of CLR 131 in certain B-cell malignancies. Specifically, investigators enrolled patients with multiple myeloma, chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).
The primary end point of the trial was clinical benefit rate. In multiple myeloma, this was defined as the percentage of patients with a stringent complete response, complete response (CR), very good partial response, partial response (PR), and stable disease (SD) per International Myeloma Working Group criteria within 3 months of the first infusion of the investigative agent. In lymphoma, this was defined as the proportion of patients with CLL/SLL, LPL, MZL, MCL, and DLBCL who achieved a CR, PR, and SD via Lugano classification CT-based response criteria within 3 months of the initial infusion of the agent. Additional end points of the trial included ORR, progression-free survival, median overall survival, as well as other efficacy markers.
Part A was the dose-exploration portion of the trial, which was done in patients with relapsed/refractory B-cell malignancies. Participants received the following 3 different total doses of CLR 131: less than 50 mCi, approximately 50 mCi, and approximately 75 mCi; the treatment was given as a single 30-minute infusion or in two 30-minute infusions on day 1 and day 7. Participants had the opportunity to receive a second dose cycle about 75-180 days after the first.
Previous results from the trial showed that CLR 131 elicited an ORR of 34.5% in patients with multiple myeloma over all doses examined (n = 33).2 The ORR with the agent was even higher, at 42%, in patients with non-Hodgkin lymphoma over all doses (n = 20). Based on these data, the study was then expanded to evaluate a 2-cycle dosing regimen of the agent. Patients will receive a total of 4 infusions that will be given on day 1 and day 15, and then again on day 57 and day 71.
With regard to safety, CLR 131 continues to be well tolerated. The most commonly reported treatment-emergent adverse effect is cytopenias. To date, no unexpected toxicities have been observed with the agent.
In May 2020, the FDA granted a fast track designation to the agent for use in the fourth line or later relapsed/refractory multiple myeloma. In July 2020, CLR 131 was fast tracked for use in relapsed/refractory DLBCL.