Cellectar Biosciences gets FDA green light for multiple myeloma clinical study

MADISON, Wis.—The U.S. Food and Drug Administration has accepted an Investigational New Drug application from Cellectar Biosciences Inc. to initiate clinical study of I-131-CLR1404, which the company is advancing in the indication of relapsed or refractory multiple myeloma.

Cellectar’s I-131-CLR1404 is a radiopharmaceutical that consists of a proprietary phospholipid ether (PLE) analog, which serves as a cancer-targeted delivery and retention vehicle, that is covalently labeled with Iodine-131, a cytotoxic radioisotope commonly used to treat thyroid and other cancers.

The company completed a Phase 1b dose-escalation trial of I-131-CLR1404 in the first quarter of this year in patients with advanced solid tumors. In the fourth quarter of this year, Cellectar intends to launch a Phase 1/2 proof-of-concept trial in roughly 20 patients with relapsed or refractory multiple myeloma that have previously been treated with or are intolerant of an immunomodulator and a proteasome inhibitor. The trial will seek to determine the safety and tolerability of I-131-CLR1404, with and without concurrent weekly dexamethasone, as well as the recommended dose for future trials. The study will also evaluate the therapeutic activity of the compound in the given patient population in terms of overall response rate, duration of response and time to progression.

“This trial affords us an opportunity to both assess the safety of I-131-CLR1404 in patients with multiple myeloma, but also to obtain near-term proof-of-concept data characterizing the activity of I-131-CLR1404 in this difficult-to-treat patient population,” Dr. Simon Pedder, president and CEO of Cellectar, said in a press release. “Having initiated a Phase 2 diagnostic imaging trial of our lead compound, I-124-CLR1404, in glioblastoma earlier in the year, we are pleased to now have this opportunity to initiate a second, company-sponsored clinical trial with the potential to showcase the therapeutic applications of our targeted delivery platform.”

Thanks to its PLE platform technology, Cellectar’s compounds are designed to be selectively taken up and retained in cancer cells, including cancer stem cells. Cellectar can attach therapeutic as well as imaging agents thanks to its platform, and its PLE platform has been shown to reliably accumulate in malignant cancer cells. I-131-CLR1404 has been designed to combine an intracellular radiation mechanism of destroying cancer cells—including cancer stem cells—via targeted delivery to malignant tissue.

As the company notes on its website, the effectiveness of their approach is due to the fact that “PLEs become trapped in malignant tumor cell membranes because tumor cells cannot metabolize and eliminate them. Non-malignant cells, however, metabolize and clear these compounds.” The company has evaluated its platform in a variety of cancers, and to day, the PLE delivery platform has proven to be selectively retained “by more than 50 xenograft, orthotopic and transgenic solid cancer and cancer stem cell-derived models.”

Cellectar attributes this effectiveness to the differences between the plasma membranes of cancer cells and those of healthy, normal cells. the membranes of cancer cells are highly enriched in what Cellectar calls “lipid rafts,” “specialized regions of the membrane phospholipid bilayer that contain high concentrations of cholesterol and sphingolipids and serve to organize cell surface and intracellular signaling molecules (e.g., growth factor and cytokine receptors, the phosphatidylinositol 3-kinase (P13K)/Akt survival pathway).” Data have suggested that these lipid rafts are the portals of entry for PLEs due to their high affinity for cholesterol, which draws them to the cholesterol-rich lipid rafts.

The National Cancer Institute ranks multiple myeloma as the second most common hematologic cancer. An estimated 70,000 people are living with this form of cancer in the United States, with some 24,000 new cases diagnosed each year, and worldwide, approximately 230,000 people have multiple myeloma, with roughly 114,000 new cases diagnosed each year.