ROR1: An Update From ASH 2017

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Topics include: Treatments

What have researchers discovered about ROR1 and its role in targeted CLL therapies? Andrew Schorr hosts coverage from the 2017 American Society of Hematology (ASH) conference to learn about the latest innovations in CLL research and treatment. Dr. Michael Choi, from the UCSD Moores Cancer Center, shares an update on ROR1 and its role in CLL. 

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Hello and welcome to Patient Power.  I'm Andrew Schorr on location at the American Society of Hematology meeting in Atlanta.  I'm with a young investigator—I love young investigators, that's our future—Dr. Michael Choi from UC San Diego where I happen to get care.  Thank you so much for being with us, Michael. 

Dr. Choi:

Thank you.  I like being called young still I guess. 

Andrew Schorr:

No, you are.  And he works with Dr. Tom Kipps, and one of the areas of research they've been doing is something called ROR1 or cirmtuzumab.  Did I get it right? 

Dr. Choi:

Yep.  That's right. 

Andrew Schorr:

And you presented data here about that.  So help us understand, what is it and what could it mean for people, for example, with CLL or maybe other conditions, too? 

Dr. Choi:

Yeah.  We are definitely excited about our work and what we've found with ROR1.  I think a long story made short is that ROR1 is a protein expressed on CLL cells, and we think it's unique because it's actually not expressed on any other normal tissues in the body.  Turns out it's a stem cell antigen or something that's involved in embryogenesis, but after development usually the body shuts off production of ROR1. 

Somehow in CLL cells and in other types of malignancies, we know mantle cell lymphoma and subsets of things like breast cancer and lung cancer and even acute leukemias, ROR1 gets turned back on, and so we think it’s something that we can target for therapy. 

At UCSD and Dr. Kipps's lab and Dr. Jamison's lab we actually made from the ground up an antibody that binds to and blocks ROR1 signaling.  They call it cirmtuzumab.  We've now actually completed our Phase I study which was designed to determine the safety of cirmtuzumab and to determine the ideal dose to go into other studies, and we're very encouraged with the results.  As one would expect based on how specifically it binds to tumor, it was a very safe drug.  There were not recurrent side effects, and there were not any dose-limiting toxicities.  It seems like it's a very clean drug. 

Andrew Schorr:

Okay.  Is this an oral medicine or an infused medicine? 

Dr. Choi:

Yes.  It's an infusion.  We are also kind of trying to determine the best way to infuse it.  We actually on the trial infused it fairly slowly, like we do with ofatumumab (Arzerra) or rituximab (Rituxan), but in future trials we'll actually try and speed that up, because we actually didn't find that there were infusion reactions. 

Andrew Schorr:

Let me see if I get this right.  So in a sense it's like turning off a light switch.  You're trying to turn off a light switch on the malignant cells without side effects or toxicities, I think you call it, for the rest of us. 

Dr. Choi:

Yeah, exactly.  Yeah, ROR1 seems like it's activating one pathway.  It's kind of one way that the cancer cells get support from their surroundings.  It's a pathway that looks like other drugs don't block, so drugs like ibrutinib (Imbruvica) do not hit this pathway.  And we think it might be one way that these cells kind of might be able to persist despite other drugs that are very active. 

So, yeah, we are trying to turn off that switch, and I think so far we've made sure that that's safe.  We've confirmed that we have indeed turned it off, and I think now our next step is to kind of just to see how we can best utilize this drug. 

Andrew Schorr:

Okay.  Phase I trial.  So what happens next?  Is there an opportunity for patients where be maybe other drugs are not working for them where they could participate in this research either at UC San Diego or elsewhere? 

Dr. Choi:

Yes.  So we're now in position to start actually our Phase I/II trials.  The approach we're going to take is to combine it with other pathway inhibitors, so kind of turning off two lights, which is hopefully that really is too much for a cancer cell to overcome.  So we're going to start a trial for patients with CLL and also patients with mantle cell lymphoma to give this drug in combination with ibrutinib. 

This will be a multicenter trial throughout the United States, so we're really excited about that.  We think this has a—it could contribute without adding toxicity. 

Andrew Schorr:

Wow.  So the idea is finding a target, which you have with ROR1.  Can there be other targets other medicines hit in sort of a one-two punch, if you will, so that the cancer cell can't get around it. 

Dr. Choi:

Yeah, that's a great way to put it, yeah.  I think of it as taking two legs out of a stool.  It doesn't leave much for the cell to stand on. 

Andrew Schorr:

Okay.  Well, as we said, of course, this is early research, but there are clinical trial opportunities that may be appropriate for you.  You want to discuss it with your doctor.  Be in touch with us at Patient Power, see if we can help.  We want to congratulate Dr. Tom Kipps, my other doctor, Dr. Jamieson, and also Dr. Michael Choi and others involved in the research.  Thanks for what you do. 

Dr. Choi:

You're welcome. 

Andrew Schorr:

We really appreciate it.  Andre Schorr with Dr. Michael Choi from UC San Diego and Moores Cancer Center.  On location in Atlanta at the American Society of Hematology meeting.  Remember, knowledge can be the best medicine of all. 

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on January 18, 2018