Update on Mosunetuzumab (Bi-specific) for Follicular Lymphoma

Finally, some interesting research to report on! You don't need to listen to my opinions about vaccines and telemedicine (at least for a few days).

At the 2021 Pan Pacific Lymphoma Conference (held in beautiful Hawaii a couple of weeks ago), there was a presentation called "Updated Experience from Mosunetuzumab in Multiply Relapsed Follicular Lymphoma: Promising Efficacy from a Phase 1 Trial."

The slides from the presentation are available here.

The presentation is an update from a phase 1 trial for Mosunetuzumab, a bi-specific. I've written about bi-specifics before, but here's a reminder. A treatment like Rituxan works because it seeks out cancer cells (B lymphocytes, specifically) that have a protein on its surface called CD20. When it finds the CD20, it attaches itself and kills the cancer cell.

A bi-specific works in a similar way, but because it is "bi" it attaches to two things -- first the cancer  cell, by finding the CD20. But it also looks for a CD3 protein, which is found on a T cell, an immune cell that can kill cancer cells (that's the "T" in CAR-T). So the bispecific might kill the cancer cell on its own (the way Rituxan would), but it also brings in the T cell to help. So, in theory, a bispecific could be twice as effective as something like Rituxan.

This presentation reports on a phase 1/2b study. Phase 1 studies usually involve a fairly small number of patients, and focus on how safe a treatment is, and how much of the treatment to give to be both safe and effective. The study involves 62 patients with FL who have had at least two previous treatments. Some of the patients were considered "high risk."

The numbers look good. There was an Overall Response Rate of 67.7% (42 of the 62), including a Complete Response from 51.6% (32 of 62). The responses for patients with high risk FL were also high.

Because the trial focuses specially on patients who have already had 2 or more treatments, the researchers are especially interested in how well Mosunetuzumab works on patients who have had specific treatments. In the study, 4 patients had already had CAR-T, and it had stopped working (they were refractory). All 4 had a response, and 2 of the 4 had a Complete Response. 

For patients who were refractory to PI3K inhibitors, the response rate was 92%, with an 84% CR.

For patients who were POD24 (that is, their disease came back within 24 months of receiving immunochemotherapy, making them very high risk), the response rate was 76%, with a 55% CR.

There were a few other breakdowns for high risk subgroups, and their numbers were equally good. 

As a phase 1/2b study, the researchers are looking at a few different things. As a phase 1 study, they are still looking at dose escalation -- figuring out how much to give a patient before it becomes too much. And as a phase 2b study, they already know it works, and are looking to create a larger, phase 3 study, which would potentially lead to approval. That's where they are headed, with a combination trial where patients will get Mosunetuzumab and Lenalidomide. Combos often work better than single agents.

I focus a lot on first-line treatments -- what a patient receives the first time they are treated after diagnosis. That seems to me like the logical place to focus for a disease like Follicular Lymphoma that is considered incurable. But treatments like Mosunetuzumab in a trial like this one are so important, too -- if they are effective for people who have already had two or more treatments, they might extend survival and improve quality of life for a lot of us. I'm past the need for a first treatment, like many of you, so trials like this one are worth paying more attention to.

Some good news during a slow summer.