CLR 131 Elicits Promising Response Rates in Triple-refractory Multiple Myeloma Trial

CLR 131, Cellectar Biosciences’ lead experimental candidate, resulted in a 40% response rate among people with multiple myeloma who failed to respond to three treatment modalities, according to additional data from the CLOVER-1 clinical trial.

These triple-refractory patients, who previously failed to respond to at least one immunomodulatory treatment, one proteasome inhibitor, and one anti-CD38 antibody, had received a total CLR 131 dose of 60 millicurie (mCi, a unit of radioactivity) or greater.

“We remain encouraged by the consistency of CLR 131’s efficacy and tolerability data in these extremely challenging to treat triple class refractory multiple myeloma patients,” John Friend, MD, Cellectar’s chief medical officer, said in a press release.

“A 40% ORR [overall response rate] is a clinically meaningful outcome,” he added, noting that two recently approved therapies for multiple myeloma showed “a 25% and 31% ORR in triple class refractory patients.”

A phospholipid drug conjugate, CLR 131 consists of CLR1404 — Cellectar’s small molecule that targets specific fat molecules, called phospholipid ethers (PLE), in the membrane of cancer cells — bound to a toxic, radioactive compound called iodine-131.

In this way, CLR 131 is expected to deliver radiation specifically to cancer cells, resulting in their death while limiting damage to healthy cells. It is being developed for the treatment of multiple myeloma and B-cell lymphomas, as well as pediatric and head and neck cancers.

Based on positive interim data from a recently-completed Phase 1 clinical trial (NCT02278315) in heavily pre-treated multiple myeloma patients, the therapy received orphan drug designation in both the U.S. and Europe, as well as fast track designation in the U.S. for the treatment of relapsed or refractory multiple myeloma.

These designations are meant to accelerate CLR 131’s development and review through regulatory support and financial benefits, as well as to provide marketing exclusivity for a period of time upon approval (seven years in the U.S. and 10 years in Europe).

The open-label CLOVER-1 Phase 2 clinical trial (NCT02952508) is evaluating the safety and effectiveness of CLR 131 in up to 80 people with a range of pre-treated B-cell malignancies, including multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The study’s main goal is to assess the proportion of patients achieving at least disease stabilization (clinical benefit) within three months following CLR 131’s first dose. Secondary goals include overall response rate (partial and complete responses), the time patients live without signs of disease progression, and median overall survival.

CLOVER-1 already has completed its Part A dose-exploration portion, which tested three different CLR 131 doses: less than 50 mCi/m^2; about 50 mCi/m^2; and about 75 mCi/m² in total. All were given directly into the bloodstream through either a single or two 30-minute sessions.

Data from the 43 people with heavily pre-treated multiple myeloma enrolled in Part A showed that the trial met its main goal in this group, with all patients achieving at least disease stabilization.

The highest response rate (42.8%) was observed among those receiving the highest dose of CLR 131. Among these patients, 85.7% showed tumor reduction, and 50% of those with high-risk disease and 33% of those with triple-refractory cancer achieved partial or complete responses.

The therapy was generally well-tolerated, with the most frequently reported adverse side effects being low counts of one or more types of blood cells.

Based on these positive results and additional data showing the potential to further improve response rates and durability, the trial was expanded to evaluate a two-cycle dosing regimen that provides a total CLR 131 dose of about 100 mCi.

People with triple-refractory multiple myeloma or lymphoplasmacytic lymphoma are currently being recruited for this Part B at about 10 U.S. cancer centers.

The newly announced data concerns a total of 15 triple-refractory multiple myeloma patients enrolled in the completed Part A of the study and in the ongoing Part B from March through May. All had received a total CLR 131 dose of 60 mCi or greater.

Six (40%) of these patients achieved partial or complete responses — a response rate considered clinically meaningful in this hard-to-treat patient population.

According to the press release, patients enrolled in CLOVER-1 continue to tolerate CLR 131 well, with no unexpected safety concerns identified and with the “most common and almost exclusive” side effect being lower-than-normal blood cell counts.

“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,” said Friend.