CLR 131 Works to Halt Cancer Growth and Lower Tumor Volume in DLBCL, Early Phase 2 Data Show

Cellectar Biosciences’ investigational radiotherapeutic compound, CLR 131, effectively halted cancer progression and reduced tumor size in people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), interim data of a Phase 2 trial shows.

These results were part of the oral presentation “Interim Evaluation of a Targeted Radiotherapeutic, CLR 131, in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients (R/R DLBCL),” at the European Society for Medical Oncology (ESMO) Congress 2019 that recently took place in Barcelona.

CLR 131, a small-molecule phospholipid-drug conjugate (PDC), selectively delivers radiation to tumor cells by binding to specialized structures in their cell membrane. This targeted approach is expected to minimize radiation exposure to healthy tissue and lower overall toxicity.

The ongoing multicenter and open-label CLOVER-1 Phase 2 trial (NCT02952508) is evaluating the safety and effectiveness of CLR 131 in people with relapsed or refractory B-cell cancers, including multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, mantle cell lymphoma, and DLBCL.

The study’s primary goal is to assess clinical benefit — the proportion of patients achieving at least disease stabilization — after a single injection of CLR 131 (delivered at 25.0 mCi/m2 dose) with the possibility of a second injection of an equal dose 75 to 180 days later.

Secondary goals include overall response rate (ORR) — the proportion of patients whose tumor is eliminated or significantly reduced, progression free survival (PFS) — or the time a patient lives without signs of disease progression, and overall survival.

The presented interim data covered six DLBCL patients who received a single 30-minute infusion of CLR 131 as, on average, their fourth-line treatment. Half of the patients achieved the primary goal of clinical benefit, with two of them responding to treatment (ORR of 33%) and one achieving stable disease.

Among responders, one person (16.6%) who was refractory to two prior treatment lines achieved a complete response, with a greater than 99% total reduction of tumor volume. Almost eight months after treatment, this patient remains a complete responder.

Another person (16.6%) with cutaneous DLBCL achieved a partial response, with a 56% reduction in total tumor volume.

At the time of interim analysis, the average duration of patients’ response was around five months, highlighting CLR 131’s durable responses.

CLR 131 treatment was also effective against both subtypes of DLBCL — germinal center B-cell (GCB) and activated B-cell (ABC) — and tumors carrying either c-Myc or B-cell lymphoma-2 (BCL-2) mutations, or both, which are associated with poor outcomes.

Results also showed that patients receiving CLR 131 at a dose ratio of 1.2% or greater relative to tumor volume had considerably longer PFS than those receiving treatment below that dose ratio.

The most frequently reported adverse events in these patients were blood-related and mild to moderate in severity, consistent with those reported in previous trials.

CLOVER-1 study, which initially planned to enroll 10 DLBCL patients, has expanded its recruitment to a total of 40 patients due to previous positive interim results. Eligible patients must have relapsed or failed to respond to chemotherapy regimens containing Rituxan (rituximab) and an anthracycline. Enrollment is ongoing at sites across the U.S.; more information is available here.

“The study remains ongoing and, based on this [group] and additional data from an ongoing dose escalation Phase 1 study, patients in the Phase 2 CLOVER-1 study are now receiving a higher 37.50 mCi/m² fractionated dose administered in two 30-minute infusions of 18.75 mCi/m²,” James Caruso, Cellectar’s president and CEO, said in a press release.

“We remain optimistic that CLR 131 has the potential to provide a meaningful treatment option for a variety of lymphoma patients and look forward to reporting additional data,” Caruso added.

Cellectar expects to report topline data before the close of 2019.

The U.S. Food and Drug Administration (FDA) has recently granted CLR 131 fast track designation for the treatment of relapsed or refractory DLBCL. CLR131 also received FDA orphan drug status as a treatment for relapsed or refractory multiple myeloma.