FDA Grants CLR 131 Fast Track Status for LPL/WM

The FDA has granted a Fast Track designation to CLR 131 for use as a treatment for patients with lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) who have received at least 2 prior treatment regimens.¹

The designation is based on findings from the ongoing phase 2 CLOVER-1 study, which is investigating CLR 131 in patients with relapsed/refractory B-cell lymphomas (NCT02952508).

“LPL/WM patients that do not respond optimally or are intolerant of ibrutinib, currently have limited treatment options and poor survival rates. Fast Track designation for LPL/WM further supports our clinical development strategy to quickly and efficiently provide these patients with an effective therapeutic alternative,” James Caruso, president and CEO of Cellectar, said in a press release.

“All 4 LPL/WM patients treated in our CLOVER-1 phase 2 study to date achieved a 100% overall response rate and a 25% complete response rate. This strong response rate may represent an important improvement in the treatment of relapsed/refractory LPL/WM as no approved or late-stage development treatments for relapsed or refractory patients have reported complete responses,” added Caruso.

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.

The FDA previously granted CLR 131 a Fast Track designation for use as a treatment for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

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.

The open-label, multicenter, phase 2 CLOVER-1 trial is enrolling 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), 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.

CLR 131 also previously received a Fast Track designation for the treatment of patients with relapsed/refractory multiple myeloma.

References

1. Cellectar Receives FDA Fast Track Designation for CLR 131 in Lymphoplasmacytic Lymphoma/Waldenstrom’s Macroglobulinemia. Published Online May 26, 2020. https://www.cellectar.com/news-media/press-releases/detail/238/cellectar-receives-fda-fast-track-designation-forclr-131. Accessed May 26, 2020.
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.