ASH Preview: Epcoritamab (Bispecific)

OK, enough about skin cancer. This is supposed to be a blog about Follicular Lymphoma. 

So let's get back to the ASH convention and what is coming up there.

It's always interesting to guess which FL presentations at conferences (if any) are going to get lots of attention by the oncology community. Occasionally, there are some blockbusters that change the way FL patients are treated (like when R-Squared trial results were announced). Most years, there isn't much that generates a lot of excitement on sites like OncLive that cover cancer news.

If I had to guess which presentation will get some attention this year, it will be this one: 1655 Epcoritamab SC Monotherapy Leads to Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: First Data Disclosure from the Epcore NHL-1 Follicular Lymphoma Dose-Expansion Cohort. 

Epcoritamab is a bispecific antibody. To remind you of what that means -- a bispecific antibody works sort of like a monoclonal antibody like Rituxan. It targets a protein on the surface of the cancer cell. In fact, Epcoritamab targets the same prtein that Rituxan targets -- CD20. But a bispecific has a second part to it ("bi" in "bispecific" means "two," so two parts to it). The second part targets the protein CD3 on T cells, a kind of immune cell. So by bringing the cancer cell in close contact with an immune cell, the bispecific helps to eliminate the cancer cell. 

There is already a bispecific approved by the FDA for FL -- Mosunetuzumab (for patients with relapsed/refractory disease who have had at least 2 treatments). Another (Odronextromab) has received priority review from the FDA. And Epcoritamab has been pretty successful, too. It has been approved in the US and UK for r/r Diffuse Large B Cell Lymphoma. And at the ASCO conference last June, some results were shared that showed a successful pairing of Epcoritamab and R-Squared. 

This research at ASH focuses on single use Epcoritamab, tested in a phase 1/2 clinical trial. It's a fairly large trial for one that is early -- 128 patients with r/r FL who have had at least 2 prior treatments. The ASH abstract makes clear that the hope is to show that Epcoritamab can work for as many patients as possible. They point out all of the different prior treatment types that patients had received -- 77% had anthracyclines (like R-CHOP), 31% had Lenalidomide, 19% had a stem cell transplant. 

Most patients (54%) were primary refractory (they never had a Complete Response to a treatment), 70% were double refractory (two treatments didn't work), and 69% were refractory to their last treatment. In addition, 42% were POD24 (their disease returned within 24 months of receiving immuno-chemotherapy). So, in short, this is a group of patients that could really use a good option.

Results were very good.  The Overall Response Rate was 82%, with a Complete Response Rate of 63%. (For the sake of comparison, the phase 2 trial that led to Mosunetuzumab's approval showed an 80% ORR and a 60% CR). More importantly, the response rates were pretty consistent across high-risk subgroups -- double refractory patients had an ORR of 76% and a CR of 56%, POD24 were 80% and 60%, etc. Patients who had 2 prior treatments had response rates of 89% and 72%; 3 prior treatments were 88% and 68%; 4 or more prior treatments were 68% and 45%.

As for safety (the most important thing being considered in a phase 1 trial), the most common side effects were Cytokine Release Syndrome (66%), injection-site reaction (57%), COVID-19 (40%), fatigue (30%), low white blood cell counts (28%), diarrhea (27%), and fever (25%). Side effects leading to stopping treatment happened to 19% of patients, the most commonly because of COVID-19. Side effects were mostly low grade.

(It's worth noting that the data here is from patients treated from  2020 to 2022, at the height of Covid. It makes sense that a treatment that compromises the immune system would result in such a high number of people stopping treatment. This is the first time I've seen Covid mentioned this way in a trial write-up.)

So overall, this is very good news. It's still a very early trial. I don't imagine an application for approval will come until there is more data (the FDA is being more careful about these things lately), but it's good news. And since bispecifics are one of the treatment types that gets oncologists most excited these days (along with CAR-T), I'm guessing it will be included in news stories and summaries about the best things that happened at the conference.

I'll try to pick out a few more gems from the abstract list. The conference is coming up pretty soon -- just a few more weeks. I'll see how much reading I can do before then.