CLR 131 (I-131-CLR1404) is an experimental treatment that Cellectar Biosciences is developing to treat different forms of cancer including myeloma.

How does CLR 131 work?

CLR 131 is a combination of Cellectar’s proprietary Phospholipid Drug Conjugate (PDC) and the radioisotope Iodine-131 (I-131). I-131 is commonly used to kill thyroid cancer cells. The PDC contains a phospholipid ether molecule that targets cancer cells.

Cancer cells generally have higher metabolic needs than regular cells. Therefore, they change their membrane structure to include more lipid rafts. This helps bring molecules inside them. Once enough of the PDC molecules have bound to a lipid raft, the cell inverts or flips the raft over, allowing the PDC molecules to enter the cells where they will accumulate and exert their action. Researchers hope that in the case of CLR 131, I-131 will accumulate and deliver radiation to the cancer cells and destroy them.

CLR 131 in clinical trials

A Phase 1 clinical trial (NCT02278315) is investigating the safety and tolerability of different doses of CLR 131 in patients with relapsed or refractory myeloma. Patients must have been treated with or become intolerant to a proteasome inhibitor and an immunomodulator, and either been unresponsive to the treatment (refractory) or had success and then have their cancer return (relapsed).

Participants receive one of seven different doses of treatment. Patients in the first four groups each receive a single injected dose of CLR 131 at a concentration of 12.5 mCi/m2, 18.75 mCi/m2, 25 mCi/m2, or 31.25 mCi/m2. All patients also receive low-dose dexamethasone (40 mg/week) for up to 12 weeks.

The results from the first four groups showed a benefit of treatment with CLR 131, especially with the highest dose. Here, all three patients had either stabilization or partial response to treatment. From these results, a fifth group of patients received the same dose of 31.25 mCi/m2 but split into two doses, a week apart in the hopes of reducing the adverse effects of the treatment.

Finally, a sixth group received two doses but at an overall dosage of 37.5 mCi/m2. This group achieved a 50% overall response rate (ORR) with two patients achieving a partial response and the other two achieving a minimal response. Researchers had also planned a seventh split-dose group of 40 mCi/m2 total but they have not yet announced results from this group.

A Phase 2 open-label clinical trial (NCT02952508), called CLOVER-1, is investigating the use of CLR 131 in patients with myeloma and several B-cell lymphomas.

The study consists of two parts. In part A, patients receive one of three doses of treatment: less than 50 mCi total body dose (TBD), about 50 mCi TBD, and 75 mCi TBD. Patients have the option to receive another dose of treatment 75 to 180 days later. A total of 43 patients with myeloma have already received treatment. They all achieved stabilization of their cancer. More than 40% of those in the highest dose group achieved a partial or complete response.

The study recruited more patients for part B of the study. This part focused only on patients with myeloma or lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia who were triple class refractory. This means that they did not respond to previous treatments of CD38 inhibitors, immunomodulatory treatments, or proteasome inhibitors.

Initial results from patients in both parts A and B who had triple class refractory myeloma and received at least 60 mCi of CLR 131 showed a 40% ORR. The study found that patients tolerated the treatment well. The main treatment-emergent adverse event was cytopenia.

The trial is still recruiting participants across the U.S. Researchers estimate the study will be completed in October 2020.

Other information

The U.S. Food and Drug Administration and the European Commission granted CLR 131 orphan drug designation for the treatment of myeloma. The FDA also granted it fast track designation for patients who have failed at least four prior lines of therapy.

 

Last updated: Sept. 30, 2020

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