Cellectar Biosciences has announced positive trial results demonstrating that its investigational therapy CLR 131 significantly reduced tumor activity, with tolerable safety, in B-cell lymphoma patients who received prior treatments.
A “notable” percentage of patients with lymphoma responded to the therapy — a total of 42% across all doses tested — and tolerated it well, according to data from the CLOVER-1 Phase 2 trial (NCT02952508).
Relapsed or refractory B-cell lymphomas are difficult-to-treat cancers, and as few as 2% to 4% of patients with forms of this cancer respond to therapies.
“The data reported today are very promising and we believe the product profile for CLR 131 can improve further with the administration of a second cycle. These results are even more impressive considering the challenging patient population tested, as all were heavily pre-treated with the vast majority being refractory to their most recent therapy,” James Caruso, Cellectar’s president and CEO, said in a press release.
“Based upon these compelling data and the need for new and innovative treatment options for patients, we plan to execute upon a well-defined and approvable regulatory path forward in a prioritized hematologic indication.”
CLR 131 (also known as I-131-CLR1404) is a small-molecule, phospholipid-drug conjugate designed to deliver radiation selectively to cancer cells, which, unlike conventional radiotherapy, is expected to limit exposure to healthy cells and minimize toxicity.
It contains a radioactive compound bound to a mixture of phospholipid ethers that binds to specialized structures in the membrane of cancer cells, allowing for selective cancer uptake. This delivers radiation directly to tumor cells, inducing their death.
The U.S. Food and Drug Administration has granted orphan drug designation to CLR 131 for lymphoplasmacytic lymphoma, a rare type of non-Hodgkin’s lymphoma (NHL), and fast track designation for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the most common form of NHL.
The open-label, multicenter CLOVER-1 trial is investigating CLR 131 in people with B-cell lymphomas who received prior treatment for their condition, including those with multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, mantle cell lymphoma, and DLBCL.
The study is being conducted in several cancer centers in the U.S. and is recruiting patients. More information about the trial is available here.
To date, the trial has included 20 lymphoma patients who had received a median of three previous lines of therapy, with some having as many as nine prior lines of therapy. Most of these patients were also resistant to treatment with rituximab and Imbruvica (ibrutinib).
Participants receive a single infusion of one of three doses of CLR 131 — lower than 50 mCi (a sub-therapeutic dose), 50 mCi, or 75 mCi total body dose — with the possibility of a second injection of equal dose 75 to 180 days later.
Current data show that the trial met its primary efficacy goal — a significant proportion of patients achieved a clinical benefit, defined as stable disease or better response — within three months after CLR 131 injection.
Among the lymphoma patients, 42% of those receiving the 50 mCi dose responded to treatment, and 43% of those on the higher 75 mCi total body dose achieved the same outcome.
Looking at lymphoma subtypes, all patients with lymphoplasmacytic lymphoma attained a response to CLR 131, including two in the 50 mCi arm and two in the 75 mCi group. One of these patients reached complete response and remains free of cancer signs nearly 27 months after the treatment.
LPL/WM is a rare, slow-growing non-Hodgkin’s lymphoma in need of better treatment options. The results obtained with CLR 131 may represent “an important improvement,” Cellectar stated, as no treatments to date have led to a complete response in patients with this form of lymphoma, who are on their second- and third-line of treatment.
Response rates were not as high in other subtypes, but were also promising: 30% in DLBCL, including one DLBCL patient with a complete response that continued for at least 24 months after treatment, and 33% among patients with CLL/SLL and MZL.
Currently, only two mantle cell lymphoma patients have been enrolled, achieving stable disease as the best response.
“For patients who have failed the current standard of care treatments for any of these indications, there is a need for additional treatment options,” said CLOVER-1 lead investigator Sikander Ailawadhi, MD, from the hematology/oncology division at the Mayo Clinic.
“These data are impressive, especially in these very difficult to treat patient populations. CLR 131 offers a very attractive safety and efficacy profile,” he added.
Results were also encouraging in the 33 patients with multiple myeloma, 76.7% of whom experienced tumor reduction with a strong dose response.
As for the treatment’s safety, the most common adverse events were lower-than-normal blood cell counts. No patients experienced heart, neurological or kidney toxicity, infusion site reactions, damage of peripheral nerves, allergic reactions, cytokine release syndrome (an acute over-activation of the immune system), damage to the cornea, or changes in liver enzymes.
Based on these and prior results, Cellectar decided to expand the study to test a two-cycle dosing optimization regimen of CLR 131 to enhance response rate and duration. Patients will receive a total of four infusions, given on days 1, 15, 57, and 71.
In addition to these findings, the company announced the successful completion of a Phase 1 safety trial in patients with multiple myeloma, which determined that all doses of CLR 13 have been safe and well-tolerated by patients.
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