ASCO: Epcoritamab and R-Squared

Finally, I'm giving you some ASCO news. A little later than usual, but I'll try to review some abstracts over the next few weeks.

As I said in my last post, there are fewer Follicular Lymphoma presentations than in the past. Not sure why, since there's plenty of FL research going on. It could be that researchers are presenting results at other conferences instead of ASCO. Or maybe, with the FDA being a little more strict about the evidence they want before they approve a treatment, researchers are holding off presenting early results. Those are just guesses from me. 

Whatever the case, there are fewer FL presentations, but still some good stuff to share.

Over the last few years, there haven't really been any big "blockbuster" presentations on FL at ASCO. The last one was probably in 2018, when the results for R-Squared were presented. R-Squared (Revlimid + Rituxan) was a big deal because it showed that it there could be a non-chemotherapy option that was just as effective as chemo, even if its side effects were just as serious (though a little bit different). There was a lot of discussion about that presentation, and we're seeing how important R-squared has been 5 years later.

This year, I've only seen one presentation that has created a lot of excitement online, on Twitter and on oncology websites. It's #7506, "Epcoritamab + R² regimen and responses in high-risk follicular lymphoma, regardless of POD24 status." Yes, R-Squared is involved. 

The research reports on results of a phase 2 clinical trial, and it involves adding Epcoritamab to R-Squared for high risk FL patients. Let's look at all of those things.

Epcoritamab is a bi-specific, a newer type of treatment that gets a lot of Lymphoma experts excited these days. It operates sort of like Rituxan and other monoclonal antibodies, which attach themselves to lymphoma cells when they find a protein on the surface called CD20. A bi-specific is different because it seeks out a second protein (CD3) on the surface of a T cell, another kind of immune cell, and attaches itself to that as well. By bringing the cancer cell and the immune cell next to each other, the bi-specific helps the immune cell destroy the cancer cell. 

By adding Epcoritamab to R-Squared, we have three different mechanisms for finding and destroying cancer cells. Of course, that also has the potential for creating three times the side effects. A few weeks ago, the FDA gave accelerated approval to Epcoritamab for some Diffuse Large B Cell Lymphomas, so it has already been through some trials.

The twist in this ASCO presentation is that the research is focusing on POD24 patients. As you might remember, POD24 stands for "Progression of Disease within 24 months." FL patients who have received successful immuno-chemotherapy (like R-CHOP or B-R), and then have their disease come back within 24 months, have a lower Overall Survival than other FL patients. About 20% of FL patients are identified as POD24, and researchers have tried to make them a priority in the last few years.

A successful trial for this combination would be a big deal for a few reasons. It would help a group of FL patients that need the help, and it would do it without traditional chemo (which many of them have probably already had anyway).

So what are the results? Very promising.

With a median follow-up of just under 1 year, the 104 patients in the trial showed a 98% Overall Response Rate, with a Complete Metabolic Response Rate of 87%. (A metabolic response rate means the response was measured by PET scan.) That's excellent. The researchers look forward to reporting results again, after some time, to see if the results are durable, and last for longer than a year.

What about safety -- did the combo create lots of side effects? The researchers call them "manageable." About half of the patients had Cytokine Release Syndrome (all of which were treated successfully)  or nerve issues. Others included fatigue and injection site reactions (the Epcoritamab is an injection, not an IV).

At this point, it seems like the combination could be an excellent option for POD24 or other high-risk FL patients. It's a phase 2 trial, so it's a little on the small side. But there's certainly good reason to expand the trial and include more patients. 

As I said, this is probably the only FL presentation from ASCO that is getting a lot of wide discussion, and it seems like there is good reason for it. Definitely something to keep an eye on, and with the success of other bi-specifics, not really surprising. 

I'll have more ASCO news soon. No blockbusters, but some interesting research to share.