I'm still sifting through some of the abstracts from ASCO and EHA from last week, and I found another one from EHA (the European Hematology Association's annual meeting): "SUROVATAMIG (AZD0486) PLUS RITUXIMAB IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA (FL): INITIAL SAFETY DATA FROM THE PHASE 3 SOUNDTRACK-F1 TRIAL."
(The EHA puts its titles in ALL CAPS.)
I don't know much about Surovatamig, which was previously known as AZD0486. I written about it only once before in the blog -- a description of a phase 1 trial that was reported on at the 2024 ASH conference. Surovatamig is a bispecific, like Epcoritamab and Mosunetuzumab. It works by attaching itself to a cancerous B cell by grabbing on to the CD19 protein on the surface, and then also grabbing on to a T cell by the CD3 protein. In this way, it brings together the cancer cell and the immune cell that can eliminate it.
The EHA presentation reports on results of a phase 3 trial called Soundtrack-F1. Let me say first of all that "Soundtrack" is a very cool name for a clinical trial. Maybe that's just because I love music so much.
Anyway, the study is looking at Surovatamig combined with Rituxan. It is a phase 3 study, with the goal of recruiting over 1000 Follicular Lymphoma patients who have not yet received teatment, though this presentation looks only at 43 of them. According to the U.S. government's clinical trials website, it has not begun recruiting trial participants in the U.S., which might be why I haven't heard much about it. Once this smaller trial is finished, the larger phase 3 trial will begin.
Still, even with only 43 patients, the researchers had some good things to present at EHA. The focus here is on safety rather than effectiveness -- reporting on the side effects experienced by the participants. The combination is interesting -- Surovatamig targets CD19, while Rituxan targets CD20. So there seems to be, at least in theory, that the two treatments would compliment each other well when used together. But any combination of treatments also means there is the possibility of doubling up the side effects.
For this study, the researchers looked at two different dose levels of Surovatamig, and divided the patients into two groups. It's very early in the trial, so median follow-up was about 6.3 months. The first group, which had a lower dose of Surovatamig, had a 95% response rate. The second group, with the higher dose, had a 100% response rate. At the time that they cut off the data to analyze it, 75% of patients in the lower dose group and 100% of patients in the higher dose group had no Minimal Residual Disease.
As for safety, 100% of patients had Treatment-Emergent Adverse Events (TEAEs), meaning side effects that develop after the treatment has been given. The most common were infusion-related reactions (36% in group 1 and 52% in group 2), mostly due to the Rituxan (not surprising to any of us who have had Rituxan). Other common side effects were fatigue (36% and 43%), muscle aches (36% and 38%) and low white blood cell counts (36% and 38%).
More serious side effects occurred in 18% of the lower dose group and 29% of the higher dose group. Cytokine release syndrome (CRS) occurred in 36% and 38% of patients and one instance of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) occurred in each of the groups.
The study was specifically designed as a "safety run-in," a smaller study to test for side effects before the larger study happens. It's interesting to me that this is happening in a phase 3 study; that kind of dose escalation (testing different doses to find the best combination of safety and effectiveness) usually happens much earlier. In this case, there wasn't much difference between the two doses in terms of safety, but there was a slightly better effectiveness with the higher dose, so that will be the recommended dose for the larger phase 3 trial.
The larger phase 3 trial will be a randomized two arm study. Half of the patients will receive the Surovatamig + Rituxan combination, and the other half will receive Immunochemotherapy (R-CVP + Rituxan maintenance, R-CHOP + Rituxan maintenance, or Bendamustine + R + Rituxan maintenance).
There are a couple of takeaways for me. The first is that Bispecifics are clearly going to be in our future as FL patients. This kind of large study isn't messing around -- they're looking for full FDA approval. Lots of newer treatments try to get accelerated approval, and they do that with smaller phase 2 trials and aiming at Refractory/Relapsed disease. This trial has neither. That tells me that Bispecifics are fully mature. Epcoritamab and Mosunetuzumab are pretty well accepted at this point.
The other thing that strikes me is the care that is being taken to focus on safety. As far as I can tell, there has not been a phase 1 or 2 trial for this combination, but that's probably because there are already known side effects for both of the treatments involved. Still, with so much already known about other Bispecifics, it's a help the the researchers to know what to look for in this type of treatment.
As always, looking at this kind of research being presented at medical conferences tells me that we have lots to look forward to. Not every treatment in a trial will ultimately be approved. In fact, less tan 10% will likely be. But there is still lots being tested, and lots of good stuff coming.