[Beacon Staff]

Potential trial of I-131-CLR1404 in myeloma

by Beacon Staff on Thu Aug 14, 2014 7:17 am

A small company in Wisconsin has applied to the FDA to conduct a trial of a novel new therapy for multiple myeloma.

The therapy, known as I-131-CLR1404, is based on a molecule (CLR1404) that tends to accumulate in cancer cells. This tendency has been used in past research to develop the chemical as the basis for potential new imaging agents for PET scans.

However, the company also is developing it as a potential cancer therapy by attaching a radioactive isotope of iodine, I-131, to the CLR1404. This isotope of iodine already is used in some cancers to treat them with radiation.

By attaching the I-131 isotope to the CLR1404, the intent is to come up with a way to get radiation primarily to cancer cells, including myeloma cells.

Cellectar, the company developing I-131-CLR1404 as a potential cancer therapy, recently announced that it has applied to the FDA to conduct a trial of the drug in myeloma patients. Up until now, it has only tested the drug in trials involving patients with non-blood cancers.

The Cellectar press release about the application to conduct a clinical trial of I-131-CLR1404 in myeloma can be found here at The Beacon,

"Cellectar Biosciences Files Investigational New Drug Application To Evaluate I-131-CLR1404 In Clinical Trials In Relapsed Or Refractory Multiple Myeloma," Cellectar press release, August 11, 2014.

Here are some key excerpts from the press release:

"I-131-CLR1404 is a small-molecule, broad-spectrum, cancer-targeted molecular radiotherapeutic that delivers cytotoxic radiation directly and selectively to cancer cells including cancer stem cells. A Phase Ib dose-escalation trial of I-131-CLR1404 in patients with advanced solid tumors was completed in the first quarter of 2014 and results presented at the American Society of Clinical Oncology (ASCO) 2014 Annual Meeting."

And this quote from Cellectar's president and CEO:

“The radio­sen­si­tiv­ity of multiple myeloma has been well established and preclinical models show pronounced uptake of our phospholipid ether (PLE) analog delivery platform and significant therapeutic response to a single dose administration of I-131-CLR1404. We believe the selective nature and prolonged retention of our agent could enable effective, localized treatment to suppress or eliminate malignant plasma cells while preserving the important functions of normal blood cells.”

Background information about I-131-CLR1404 can be found at the Cellectar website here,

http://cellectar.com/rd-pipeline/therapeutic/

and this page at the website has previous conference presentations and publications related to the drug

http://cellectar.com/rd-pipeline/therapeutic/i-131-clr1404-posters-publications/

Keep in mind that the recent announcement by Cellectar is that it has applied to conduct a trial of I-131-CLR1404 in multiple myeloma patients. There is no guarantee the application will be approved by the FDA.

Also, as best we can tell, there are no publicly available results of preclinical tests of the drug in myeloma. Cellectar's president suggests in the press release quote above that the company has done such preclinical work. But we've not been able to find the results in either conference presentations or published research papers.

Finally, the approach the company is taking to treating cancer with I-131-CLR1404 is quite novel. While there are cancer therapies currently approved by the FDA that involving delivering radioactive isotopes to cancer cells, those therapies use approaches that are a bit different from how I-131-CLR1404 would get radiation to cancer cells.

Of course, the fact that the approach is different than existing approaches is one thing that makes I-131-CLR1404 interesting.

(Thanks to forum member Multibilly for giving us a heads up about this development.)

[dnalex]

Re: Potential trial of I-131-CLR1404 in myeloma

by dnalex on Thu Aug 14, 2014 9:10 am

This is very interesting!

[Multibilly]

Re: Potential trial of I-131-CLR1404 in myeloma

by Multibilly on Thu Aug 14, 2014 9:39 am

I think it's brilliant, in theory. Imagine the idea of being able to irradiate only specific myeloma cells? I'm so encouraged that there is so much work being done on highly targeted treatments for multiple myeloma, whether it be this approach or through the use of monoclonal antibodies, etc.

Here's a bit more background on it (Novelos changed their name to Cellectar earlier this year).

http://cellectar2014.mhwebstaging.com/wp-content/uploads/2014/02/Novelos-PR-HOT-Ph1b-1st-Cohort-5-15-12.pdf

[Beacon Staff]

Re: Potential trial of I-131-CLR1404 in myeloma

by Beacon Staff on Fri Sep 05, 2014 4:59 am

Just a quick update for everyone about I-131-CLR1404... Cellectar's application to the FDA to conduct clinical trials of I-131-CLR1404 in myeloma patients has been approved. The company plans to start a small, Phase 1/2 trial of the drug in the fourth quarter of this year.

More information about this news can be found in a company press release that was issued yesterday:

"Cellectar Biosciences Announces Acceptance Of Investigational New Drug Application To Evaluate I‑131‑CLR1404 In Clinical Trials In Relapsed Or Refractory Multiple Myeloma," Cellectar press release, September 4, 2014 (at The Beacon)

[Beacon Staff]

Re: Potential trial of I-131-CLR1404 in myeloma

by Beacon Staff on Wed Apr 15, 2015 1:21 pm

Another update ... Cellectar's trial of I-131-CLR1404 is now recruiting patients. This was announced in a press release from the company earlier today, which you can find here:

"Cellectar Biosciences Initiates Proof-Of-Concept Trial Of I-131-CLR1404 In Multiple Myeloma" (Cellectar press release issued April 15, 2015)

Additional details about the trial, including locations where it is being carried out, can be found in the trial description at clinicaltrials.gov:

https://clinicaltrials.gov/ct2/show/NCT02278315

[Nancy Shamanna]

Re: Potential trial of I-131-CLR1404 in myeloma

by Nancy Shamanna on Wed Apr 15, 2015 5:22 pm

I-131-CLR1404 is a small-molecule, broad-spectrum, cancer-targeted radio­phar­ma­ceutical comprised of a proprietary optimized phospholipid ether (PLE) analog, acting as a cancer-targeted delivery and retention vehicle, covalently labeled with iodine-131, a cytotoxic radioisotope that is already commonly used to treat thyroid and other cancer types. I-131-CLR1404 is engineered to combine an intracellular radiation mech­a­nism of cancer cell killing with targeted delivery to a wide range of malignant tumor types. Preclinical models have also demonstrated selective uptake and retention in cancer stem cells, suggesting the potential for longer lasting cancer remission. I-131-CLR1404 has been granted orphan drug designation from the U.S. Food and Drug Administration for the treatment of multiple myeloma.

I think it is interesting that iodine-131, which is already used to treat thyroid cancer, is in a myeloma clinical trial. Anecdotally, I have hear that thyroid cancer is the easiest cancer to treat, since it responds well to the radioactive iodine treatment.

I don't understand how the cytotoxic radioisotope, I-131-CLR 1404, would attack the myeloma cells. I have heard of clusters of differentiation, such as CD38, which are on the surfaces of myeloma cells, being targeted by antibody therapy. Is this similar to that mechanism?