FDA Grants Fast Track Designation to CLR 131 in DLBCL

James Caruso

James Caruso

The FDA has granted a fast track designation for CLR 131 as a potential treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).¹The designation was based on data from the DLBCL cohort of the ongoing phase II CLOVER-1 trial 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. 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,” James Caruso, president and CEO of Cellectar Biosciences, the company developing CLR 131, said in a statement.

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 that is radiolabeled with the isotope iodine-131.

Interim results from the DLBCL cohort of the CLOVER-1 trial were announced a year ago. CLR 131 induced an overall response rate (ORR) of 33% in patients with DLBCL and a clinical benefit rate (CBR) of 50% after a single administration of 250 mCi/m²of CLR 131 intravenously. Tumor reduction was seen in 60% to >90% of patients.²

Following these positive results, the company 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/m²fractionated 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 CLOVER-1 trial is an open-label, multicenter, phase II trial that is continuing to enroll patients with select relapsed or refractory B-cell malignancies. Previously treated patients with multiple myeloma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and DLBCL are eligible for enrollment. Patients with transformed DLBCL were also allowed to enter the trial.

Patients with multiple myeloma were required to have received at least 2 prior lines of therapy, including at least 1 approved proteasome inhibitor and at least 1 approved immunomodulatory drug with or without maintenance. Patients with CLL/SLL, LPL, or MZL had to have received at least 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 at least 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 toCLR 131 for the treatment of patients with relapsed/refractory multiple myeloma. The agent has 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.