FDA Grants Fast Track Designation to CLR 131 for DLBCL

The FDA has granted a fast track designation to CLR 131 for use as a treatment for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).¹

The designation is based on findings from a DLBCL cohort that is part of the ongoing phase II CLOVER-1 study, which is investigating CLR 131 in patients with relapsed/refractory B-cell lymphomas (NCT02952508).

"We are pleased to receive FDA's fast track designation for CLR 131," James Caruso, president and CEO of Cellectar Biosciences, the company developing CLR 131, said in a press release. "This designation supports our efforts to more rapidly provide a new therapeutic option for patients with relapsed or refractory DLBCL, a disease that typically has a very poor prognosis and low rates of survival."

CLR 131 is a small-molecule radiotherapeutic phospholipid-drug conjugate that directs cytotoxic radiation to cancer cells and cancer stem cells. The drug conjugate consists of the CLR1404 cancer-targeted small molecule compound, which is radiolabeled with the isotope iodine-131.

Interim results from the DLBCL cohort of CLOVER-1 were announced in 2018, which demonstrated that CLR 131 elicited a 33% overall response rate (ORR) in patients with DLBCL and a 50% clinical benefit rate (CBR) following a single administration of 250 mCi/m² of CLR 131 intravenously.² Moreover, tumor reductions were observed in 60% to >90% of patients. Following these data, Cellectar Biosciences expanded the DLBCL cohort to include an additional 30 patients.

"Dosing in the phase II CLOVER-1 study has increased, and patients are now receiving 37.5 mCi/m² fractionated in 2 administrations of CLR 131. We are optimistic that CLR 131 has the potential to provide a meaningful treatment option for these patients and look forward to additional data in 2019," Caruso added.

The open-label, multicenter, phase II CLOVER-1 trial is continuing to enroll patients with select relapsed/refractory B-cell malignancies. Patients are eligible for enrollment if they have received prior treatment for multiple myeloma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and DLBCL. Patients with transformed DLBCL were also allowed to enter the trial.

Patients with multiple myeloma were required to have received ≥2 prior lines of therapy, including ≥1 approved proteasome inhibitor and ≥1 approved immunomodulatory drug with or without maintenance. Patients with CLL/SLL, LPL, or MZL had to have received ≥2 prior regimens, which could include chemotherapy, an anti-CD20 antibody with or without maintenance therapy, and targeted therapy. In the MCL cohort, patients were required to have received ≥1 prior treatment regimen. For those with DLBCL, patients were required to have relapsed on, be refractory to, or intolerant of combination chemotherapy that includes rituximab (Rituxan) and an anthracycline.

Across the B-cell cancer cohorts, patients received either a single dose or multiple doses of CLR 131. The primary endpoint of the trial is CBR and secondary endpoints include ORR, time to progression, and overall survival. The investigators expect to enroll 80 patients in the trial.

A fast track designation has already been granted to CLR 131 for the treatment of patients with relapsed/refractory multiple myeloma, and the agent also received an orphan drug designation for the treatment of pediatric patients with osteosarcoma.

References

1. Cellectar Receives FDA Fast Track Designation for CLR 131 in Diffuse Large B-Cell Lymphoma [press release]. Florham Park, NJ: Cellectar Biosciences; July 9, 2019. https://bit.ly/2Y1RfvD. Accessed July 9, 2019.
2. Cellectar Reports Positive Phase 2 Interim Data for CLR 131 in Relapsed/Refractory DLBCL Patients [press release]. Florham Park, NJ: Cellectar Biosciences; July 18, 2018. https://bit.ly/2Nt0LyW. Accessed July 9, 2019.