Saturday, June 11, 2022

ASCO: Mosunetuzumab (EC Approval + ASCO)

 I still have a few ASCO abstracts that I want to write about, but I'm skipping ahead to this one: "CELESTIMO: A phase III trial evaluating the efficacy and safety of mosunetuzumab plus lenalidomide versus rituximab plus lenalidomide in patients with relapsed or refractory follicular lymphoma who have received ≥ 1 line of systemic therapy."

It's actually not a presentation that reports on results. Instead it's more of an announcement that a phase 3 clinical trial is coming. More on that in just a minute. 

The reason I was interested in this ASCO presentation/announcement is because this week, the European Commission approved Mosunetuzumab for Follicular Lymphoma patients who have already had two other treatments.

Mosunetuzumab is a bispecific. I've written about bispecifics before, but here's a brief reminder: I bispecific is kind of like monoclonal antibody like Rituxan. It looks for B cells that have a CD20 protein on the surface and grabs onto them -- the same thing that Rituxan does. However, the bispecific also looks for T cells that have a different protein (CD3) on their surface, and grabs onto that. This way, the bispecific brings the cancer cell close to the immune cell that can kill it off. 

It's a treatment that got my oncologist excited a couple of years ago when I asked him about what was new in Lymphoma treatments, and it's probably up there with CAR-T as the treatment that gets Lymphoma specialists most excited. 

Which is why lots of discussions about Mosunetuzumab compare it to CAR-T, like this one from Fierce Pharma, which points out that it is very effective, has tolerable side effects (like treatable Cytokine Release Syndrome), but can be given immediately, unlike CAR-T, which has to be manufactured specially for each patient. 

The EC approval is based on phase 1/2 trial results. In that trial, the Overall Response Rate was 80%, including a 60% Complete Response Rate. The median duration of response (how long it kept working) was almost 23 months. About 39% of patients had Cytokine Release Syndrome, all of which was resolved by the end of treatment. Other side effects included lower blood counts, fever,  and headache.

Getting back to the ASCO announcement: The phase 3 trial will look at Mosunetuzumab and Lanalidomide (also known as Revlimid). Half of the patients in the trial will receive that combination, and the other half will receive Lenalidomide + Rutuxan, also known as R-squared.

This should be a great trial. R-Squared, as you know if you've been paying attention to these things, is a big deal because it was the first FL treatment that was as effective as traditional chemotherapy for FL patients. It had a different set of side effects, but was as effective. It was seen as the start of a new era in FL treatment, one where we could move away from chemo.

In this phase 3 trial, the researchers will do a direct comparison between R-squared and a bispecific + Rituxan. That direct comparison is really important in a trial. It doesn't look back at an earlier study and compare. It makes sure everyone in the two parts of the trial are as similar as possible.

It will take a while to run the trial, analyze the results, see if the responses last, and then go through an approval process. So it will be a few years before any of outside of the trial can receive this combination -- and maybe we will never be able to, if the trial is unsuccessful.

But in the meantime, FL patients in Europe have a new arrow in their quiver, a new treatment option, if it seems right for them. I'm looking forward to seeing just how popular a choice it becomes.

(More ASCO commentary soon.)

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