Lonza 2024

While many chemotherapeutic agents are available to treat cancer, they come with the disadvantage of damaging healthy, normal cells in the body. This damage results in significant morbidity and can limit the amount of chemotherapy that can be safely delivered.

In the last decade, targeted therapies have been replacing standard cancer treatments like chemotherapeutics, due to their ability to specifically target cancer cells while leaving healthy cells unharmed.

Targeted therapies aim for cancer cells by focusing on molecular targets that make the chemistry of tumor cells different from that of healthy tissue. This allows for more powerful payloads to be used, which becomes especially important for recurrent or refractory, hard-to-treat cancers that are not responding to treatment, or that need an increased potency of a drug payload that would not be tolerable without a tumor-targeting delivery system.

CLR 131
Recently, promising results have been shown in a clinical trial for the novel therapeutic CLR 131, a phospholipid drug conjugate, or PDC, when used in advanced, refractory or recurrent multiple myeloma. Multiple myeloma is a cancer of the plasma cells in the bone marrow. An estimated 30,280 adults in the US will be newly diagnosed with the disease this year.[1]

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Cellectar Biosciences has announced an updated median overall survival of 26.6 months from a CLR 131 phase I trial in patients with recurrent or refractory multiple myeloma. While there are currently no head-to-head studies that have been done with CLR 131, the median overall survival observed with the three most recently FDA-approved third line therapies for multiple myeloma range from 11.9-18.6 months.

Phospholipid-Drug Conjugates (PDCs)
CLR 131 is built upon Cellectar’s patented delivery and retention platform of optimized phospholipid ether-drug conjugates, or PDCs.

The basis for this novel technology relies on the differences between tumor cell plasma membranes from those of healthy cells. The plasma membranes of cancer cells have a high level of lipid rafts, which are glycolipoprotien microdomains that contain high levels of cholesterol and sphingolipids.

PDCs are able to selectively target cancer cells based on their membranes chemistries, and therefore target tumors while leaving healthy cells unharmed. This allows for more potent drug delivery, with the reduction of harm to surrounding tissues.

CLR 131 uses the PDC delivery system to deliver iodine 131, a cytotoxic radioisotope, directly cancer cells. Thus far, PDCs have demonstrated highly selective uptake and retention in several cancers, even when seen in sites of metastases. Cellectar’s phospholipid ether (PLE) carrier platform is designed to be able to use different drug payloads in order to develop novel targeted therapies for a wide array of cancers.

Phase I Trial Results
While this trial remains ongoing, the results thus far are impressive. The first cohort of heavily pretreated myeloma patients, who had an average of 5.8 prior lines of therapy, received a single 30 minutes infusion of 12.5mCi/m2. These patients saw a median overall survival of 26.6 months. The second cohort, which received a single dose of 18.75 mCi/m2, now have reached a median overall survival of 15.4 months to date. The third cohort, patients who received 25 mCi/m2, are currently at a 10-month median overall survival to date. [2]

CLR 131 is also being currently evaluated in phase II clinical trial for relapsed or refractory multiple myeloma and select relapsed or refractory lymphomas with either one or two dose treatments. Cellectar currently has an orphan drug designation from the FDA for CLR 131 in the treatment of multiple myeloma. CLR 131 is also currently being evaluated in a Phase II clinical study to assess efficacy in a range of B-cell malignancies.[3]

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