Glofitamab: Bispecific for Follicular Lymphoma

Some exciting news from the world of Lymphoma this week. A bispecific had some excellent results in a phase 1 clinical trial. 

The results were published in The Journal of Clinical Oncology article called "Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell–Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial." 

Some background first. A bispecific is a treatment that connects to two different cells (which is where the "bi" comes from in the name). Think of Rituxan, the monoclonal antibody. It attaches itself to the CD20 protein on a B cell (the kind of cell that turns cancerous in Follicular Lymphoma). Very effective for lots of people. Now imagine something like that, but double-ended. One side can find a protein on a cancer cell and stick to it. But the other side can also find a cell and stick to it. In this case, a T cell, the kind of immune cell that kills invaders. The bispecific acts as a way to bring the cancer cell, and its worst enemy, right next to each other. A very cool idea.

And a very effective one, apparently. There are a few different bispecifics being tested  in trials for blood cancers. This one, called Glofitamab, works as I just described. That "-mab" on the end shows that it is a Monolonal Antibody, and it connects to the same protein as Rituxan does (CD20). But it also connects on the other end to the protein CD3, found on T cells. 

T cells can be very powerful, as long as they can figure out that cancer cells shouldn't be ignored. (The "T" in CAR-T stands for "T cell.")

 The study described in the article is a phase 1 trial, meaning its main focus was on "dose escalation" -- figuring out how much of the treatment to give to be most effective while staying safe. There were patients with lots of different blood cancers in the trial, mostly aggressive (like DLBCL and transformed FL), but with some indolent FL as well.

In an interview with the lead researcher, he pointed out that the treatment seemed to be even more effective as they increased the dose, while keeping side effects manageable. Patients in the trial were first given Obinutuzumab to cut down on the number of cancer cells, and then given the Glofitamab.

The Overall Response Rate was 53.8%, including Complete Responses in 36.8%. Different types of lymphoma had different response rates. Transformed Follicular Lymphoma's ORR was 41.4%, but indolent FL had a response rate of 70.5%. That's excellent.

Of course, there were side effects. Cytokine Release Syndrome was a problem for about half of the patients, with severe CRS in a small number (3.5%). Five patients had to withdraw because of serious side effects. Other side effects included nerve issues and low blood counts, which are common in blood cancer treatments.

The lead researcher is optimistic that this treatment could eventually be as effective as CAR-T, though less expensive, since it is "off the shelf," while CAR-T needs to be manufactured specially for each individual patient.

I like optimism, but a phase 1 trial is a long way away from the doctor's treatment room. I hope he's right. We'll have to wait and see.

The phase 2 trial will use the dose that was most effective in the phase 1 trial. There may be separate trials for the different types of lymphoma being studied.

I have a feeling this bispecific, and some others, will be a big topic of conversation at the ASCO conference in a few months. Which I'm excited about, since it will be online ad I'll be able to attend again this year!