ASH Preview: Bispecifics for Follicular Lymphoma

More on what's happening at ASH this weekend. 

William asked in a comment what I found interesting with bispecifics. There's actually a lot of bispecifics research being presented, some on new treatments, some on treatments that have been in trials for a while. But it's safe to say that bispecifics and CAR-T are still the treatments that get lymphoma experts the most excited these days.

As a quick reminder: bispecifics act sort of like monoclonal antibodies, in that they find a protein on a cancer cell (like CD20) and attach to it. But unlike a monoclonal antibody, they have two sides (that's the "bi" in the name), and the other side attaches to a protein on a T cell (an immune cell), allowing the T cell to eliminate it.  Very effective, and pretty safe.

Right now, there are not any bispecifics approved for use with Follicular Lymphoma in the U.S. The closest we have is Mosunetuzumab, which is currently under review by the FDA, though it has been approved by the EU. The FDA set a target date of December 29 for a decision, so we may hear something soon.

In the meantime, there are a few interesting presentations on Mosunetuzumab at ASH. For example, "610 Mosunetuzumab Monotherapy Demonstrates Durable Efficacy with a Manageable Safety Profile in Patients with Relapsed/Refractory Follicular Lymphoma Who Received ≥2 Prior Therapies: Updated Results from a Pivotal Phase II Study." The phase II clinical trial results are what the FDA will base its decision on, so this update is important. And the results are very good -- the Overall Response Rate was 77.8%, and Complete Response was 60%. And 79.5% of those with a CR remained in remission for 24 months. This treatment was given to patients with 2 or more previous treatments. When the researchers compared the results to the patients' previous treatments (chemo, PI3K inhibitors, CAR-T, or R-squared), the bispecific treatment had a better response rate, Progression-Free Survival, and time to next treatment. And in this update, there were no new major safety issues. It's easy to see why people are excited about it.

There will also be a description of a trial using Mosunetuzumab and Lenalidomide (no results yet). And in another presentation, a subcutaneous version of Mosunetuzumab is shown to be effective and safe. (Subcutaneous means it can be given under the skin, as a "shot," rather than as an IV.)

There are other bispecifics for FL that are getting attention at ASH. 

Plamotamab, for example, showed good effectiveness and safety in a phase 1 trial.

Epcoritamab is being tested on R/R Follicular Lymphoma in a phase II trial. (This is a subcutaneous bispecific.) It is also being tested in combination with R-squared.

Odronextamab is another bispecific with high response rates for FL in a phase II trial.

So, to sum things up, there might not be anything that is really game-changing about bispecifics at ASH this year. But instead of one big impressive presentation, there are a whole lot of very good presentations about bispecifics that show that it is a treatment that will probably be with us for a very long time. That's certainly the story that many are telling -- the future of FL will revolve around CAR-T and bispecifics, and since bispecifics are probably going to be less expensive, and thus maybe more popular.

Of course, we still don't have an approved bispecific in the U.S., and no real long-term data for effectiveness and safety. I'm kind of seeing shadows of PI3K inhibitors -- lots of excitement, priority review and approval, and lots of variations. And we know how that worked out. 

But I'm more optimistic about bispecifics. As a reminder, I'm no expert -- I'm not a medical doctor or  a cancer researcher. But it seems like 25 years of monoclonal antibody research might matter, since bispecifics work by a similar mechanism.

Lots to be hopeful about.

More ASH previews soon.