New Bispecific for FL: TNB-486

I don't usually report much on the European Hematology Association Congress, the annual meeting for blood cancer specialists in Europe. That's only because it comes right around the same time as ASCO, in early June, and especially for the last few years, I have better access to ASCO information than any other big cancer conference.

But sometimes there is a presentation from EHA that is worth taking the time to look at. OncLive had an interview last month with Dr. Ryan Jacobs, who talks about one of the presentations at EHA. The focus is on a new bispecific called (for now) TNB-486. 

As a reminder -- a bispecific antibody is sort of like Rituxan, in that it finds and attaches itself to a protein on the surface of the cancerous B cell. Rituxan attaches itself to the protein CD20, but this one attaches itself to CD19. However, a bispecific also attaches itself to another cell (the "bi" means "two"), usually a T cell. T cells are immune cells that are very powerful, but don't recognize cancer cells as "bad," since they are just other cells from the same body. But because the bispecific attaches to a protein on the T cell (in this case, CD3), it puts the powerful immune cell right next to the cancer cell, allowing the T cell to destroy the cancer cell. 

So this bispecific is a little bit different than Mosunetuzumab, which has already been approved for Relapsed and Refractory Follicular Lymphoma. Mosunetuzumab attaches to CD20, not CD19, though both of them target CD3 on the T cells. It also attaches to the T cell with "less avidity" (to use Dr Jacobs' word) -- less "enthusiasm" -- which might lead to fewer dangerous side effects.

The EHA presentation reported on a phase 1 trial, which means it had relatively few patients in it (just 17), and focused mostly on dosage -- how much would result in the most effectiveness with the fewest side effects.   

The effectiveness was great -- 91% of the patients had a Complete Response. Because this trial focuses on R/R patients -- those whose last treatment stopped working, or never worked at all -- the researchers are especially interested in how this could benefit patients who are running out of options. So they looked at "heavily pre-treated patients" (those who already had at least 3 other treatments). All 12 of them had a Complete Response. Also the 2 patients who were CD20 negative (and so can't be treated with Rituxan or Obinutuzumab or Mosunetuzumab, for example) also had a CR. And so did the 5 patients who were POD24 (who had immuno-chemotherapy and had their disease return within 24 months). And the 6 month Progression Free Survival was 91%. Overall, some excellent numbers for effectiveness.

As for safety, the numbers were also good. Because bispecifics have been around for a little while, researchers knew what to expect. The most common side effect was Cytokine Re;ease Syndrome (11 of the 17 patients). No patients had to stop the trial because of side effects, though there was one death among the patients. This was because of Covid-19, rather than because of a reaction to the bispecific (in fact, the patient had already received a CR).

As I have said many times, it seems like most of the excitement in the lymphoma community these days comes from two types of treatments -- CAR-T and Bispecifics. Both have had variations been approved for use, and both have newer variations in the pipeline that (hopefully) are more ffective and safer.

Definitely something to keep an eye on.