CLR 131 Continues to Show Encouraging Responses in Triple Refractory Multiple Myeloma

CLR 131 induced a clinically meaningful objective response rate (ORR) of 40% as treatment of patients with multiple myeloma who are triple class refractory, meaning they have become refractory to prior treatment with an immunomodulatory agent, proteasome inhibitor, and an anti-CD38 antibody, in the phase 2 CLOVER-1 clinical trial (NCT02952508), according to a press release from Cellectar Biosciences, developer of the drug.¹

The CLOVER-1 study was designed to determine the efficacy and safety of CLR-131Part A was a dose-exploration portion, which was completed in patients with relapsed/refractory B-cell malignancies, and part B is now enrolling patients into expansion cohorts. Part B will evaluate ≥ 60 mCi total body dose and 2 cycle doses based on the clinically meaningful response and predictable safety profile of CLR 131 observed in relapsed/refractory patients with multiple myeloma, as well as those with lymphoplasmacytic lymphoma (LPL) or Waldenström’s macroglobulinemia (WM).

Fifteen patients were enrolled in Part A and of those patients, the 6 who had achieved a response were triple refractory and were heavily pretreated for an average of 9 prior multi-drug regimens. Additional patients have enrolled to part B between March and May 2020, in which all patients must be triple refractory.

“We remain encouraged by the consistency of CLR 131’s efficacy and tolerability data in these extremely challenging to treat triple class refractory multiple myeloma patients,” said John Friend, MD, chief medical officer of Cellectar Biosciences, in a statement. “A 40% ORR is a clinically meaningful outcome. For reference purposes, 2 recently approved drugs received a 25% and 31% ORR in triple class refractory patients.”

Overall, 3 patients were given a total administered dose of greater than 60 mCi while 3 receives less than 60 mCi. The data were consistent with the previously released findings from February 2020, in that patients who received more than 60 mCi had strong responses to CLR 131. Patients continued to tolerate treatment well, the most common and almost exclusive treatment-emergent adverse events being cytopenias. There were no unexpected AEs.

According to the update from February 2020, the small molecule phospholipid drug conjugate had induced an ORR of 34.5% across all therapeutic doses in patients with multiple myeloma, and tumor reduction was observed in 76.7% of this patient population.²

Overall, the most common grade ≥3 adverse events (AEs) were thrombocytopenia (65%), neutropenia (41%), leukopenia (30%), anemia (24%) and lymphopenia (35%). No cases of neurotoxicity, cardiotoxicity, infusion site reaction, peripheral neuropathy, allergic reaction, cytokine release syndrome, keratopathy, renal toxicities, or changes in liver enzymes were observed.

To be included in the CLOVER-1 study, patients must have histologically or cytologically confirmed diagnosis of myeloma, chronic lymphocytic leukemia/small lymphocytic leukemia, LPL, marginal zone lymphoma, WM or diffuse large B-cell lymphoma. Patients must also have an ECOG performance status of 0 to 2, a life expectancy of at least 6 months and adequate lab values.

Patients with multiple myeloma are required to have progressive disease and at least 2 prior lines of therapy, which must include at least 1 proteasome inhibitor and at least 1 immunomodulatory agent. The study excludes individuals who had prior anti-cancer therapy within 2 weeks of initial CLR 131 infusion and those who had prior radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2 weeks of eligibility-defining bone marrow biopsy. Patients are also excluded due to certain toxicities and commodities that may have interfered with treatment.

In May 2019, the agent received a Fast Track designation for the treatment of patients with relapsed/refractory multiple myeloma in the fourth- or later-line setting. More recently, CLR 131 received an Orphan Drug designation from the FDA for the treatment of patients with LPL in January 2020. A Fast Track designation was also granted to CLR 131 as a potential treatment option of patients with relapsed/refractory diffuse large B-cell lymphoma in July 2019.

“We look forward to the further development of CLR 131, a first in class phospholipid radio conjugate that may provide a significant benefit to patients and treatment alternative for clinicians," stated Friend.¹

_References

_{1. Cellectar reports data on CLR 131 phase 2 CLOVER-1 study in triple class refractory multiple myeloma patients. News Release. Cellectar Biosciences, Inc. September 9, 2020. Accessed September 9, 2020. https://bit.ly/35g2hjY​}

_{2. Cellectar Biosciences announces CLR 131 achieves primary efficacy endpoints from its phase 2 clover-1 study in relapsed/refractory b-cell lymphomas and completion of the phase 1 relapsed/refractory multiple myeloma dose escalation study. News Release. Florham Park. February 19, 2020. Accessed September 9, 2020. https://bit.ly/2V4OaZD}