Unpacking the EPCORE NHL-1 Trial and Epcoritamab’s Promise in R/R LBCL

The EPCORE NHL-1 trial showed a 41% complete response rate with epcoritamab for patients with relapsed/refractory LBCL.

Results from the phase 2 EPCORE NHL-1 trial (NCT03625037) were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting the use of epcoritamab-bysp (Epkinly) for patients with relapsed/refractory large B-cell lymphoma.

Julie M. Vose, MD, MBA, the George and Peggy Payne Distinguished Chair of Oncology, the chief of the Division of Oncology and Hematology, and a professor in the Division of Oncology and Hematology at the University of Nebraska Medical Center, and co–editor in chief of ONCOLOGY®, spoke about the results of the trial, which had a complete response (CR) rate of 41%.

By the second assessment at week 12, 97% of patients had a response. The median duration of CR was not reached, but an estimated 96% of patients remained in CR for 3 years, with the longest ongoing CR for longer than 43 months.

What was the rationale for the EPCORE NHL-1 trial?

EPCORE NHL-1 was a study for a CD3xCD20 bispecific antibody, epcoritamab, for patients who have [progressed on 2] or more prior therapies with large B-cell lymphoma. [Patients] typically had an induction therapy, sometimes a transplant, or other secondary therapies. Some patients had [progressed on] up to 8 or 9 therapies, but the median was 3 prior therapies. The rationale behind this [study] was to come up with alternative therapies for patients who have [progressed on] standard chemotherapies, [that is], immunotherapies that have less toxicity, perhaps are easier to give as an outpatient, and that patients can continue to benefit from.

What was important about the design of this analysis?

Patients included in the study had [progressed on] multiple prior therapies for large B-cell lymphoma. They had a standard of care and then had at least [2 lines], but many times up to several prior therapies. These patients don’t have a lot of options. These patients mostly had [progressed after] either transplant, CAR T-cell therapy, or other standard therapies in addition to that, and didn’t have a lot of good options left. This study was trying to look at that patient population to see what additional therapies we could use for them, especially in the outpatient setting. Patients were treated in this study with a subcutaneous dosing, which is more convenient for patients and can typically be done in an outpatient [setting] for some of the initial smaller doses. [For] the first full dose, patients are typically admitted for that.

What were the results of this study?

The CR rate was [41%]. This analysis was a little bit different in that we were looking at patients who were still in remission at 2 years after initiating therapy. The subset analysis was to see what happened to those patients beyond the 2 years. At the 2-year mark for those patients who were in a CR, looking further at a 3-year time frame, 96% of those patients were still in CR and had maintained that during that time period. This was a different type of analysis, looking at those long-term patients who benefited from the treatment.

What was the adverse effect (AE) profile noted in this study?

The major AE from this treatment overall was cytokine release syndrome, which is typically seen in the first few doses, particularly the first full dose, which is the third dose in this regimen. Neurologic toxicity was seen very sparingly and at low grades. [Patients] didn’t see many high-grade neurologic toxicities in this particular regimen. The cytokine release syndrome is typically able to be prevented with premedication and/or treated as appropriate, but the patients are hospitalized for that first full dose, just for safety reasons.

Other AEs noted with this particular regimen would be site injection redness, [because] it’s subcutaneous, and infections. For those patients who stay on [treatment] long term, they’re particularly B-cell depleted, and because they’ve also been through a lot of other therapies, sometimes T-cell depleted; they do have a bit higher rate of infections. Unfortunately, this study was done during the time of the COVID-19 [pandemic], so there were some COVID-19 infections as well as other respiratory or viral illnesses. Very few were bacterial, but mostly viral.

How do these results underscore the potential benefits from this treatment?

[Regarding] patients in this study and patients that we have in clinical practice, if they’ve [progressed on] initial therapy, transplant, or CAR T-cell therapy, they don’t have a lot of good options. Typically, their chemotherapy is refractory by that time, and they’ve usually received multiple other immunotherapies, so they don’t have a lot of good options. This is an entirely different class of agents, and for those patients who do get a CR, it’s durable and well tolerated. It’s a very important alternative treatment for this patient population.

Are there any other analyses planned for this trial?

Additional analyses are being done to look at circulating tumor DNA [ctDNA] testing, which is an important way for us to look for minimal residual disease. A high percentage of patients who were in clinical remission also had ctDNA-negative testing. For those patients who had both negative clinical testing and negative ctDNA, those were the patients who seemed to benefit from this treatment and seemed to stay in remission long term. Those tests are continuing to be done on those patients in the long term, and [we are] trying to look at the relapse rate even after the drug is stopped. There’s a lot more testing and a lot more evaluation to be done.

How do novel analysis findings shape personalized treatment strategies for this patient population?

These findings show that we do have alternatives for those patients now that are relatively well tolerated and have a high CR rate. Those patients who are in a CR tend to stay in CR if it’s molecularly—and by PET or other scanning—negative. It’s a good alternative for those patients, and eventually, they get down to less frequent dosing and toxicity after the first cycle is well tolerated. It’s a good alternative for those in certain patient populations.

How did demographics and disease features among patients with a CR at 2 years differ compared with the intention-to-treat population?

The patients who were in CR at 2 years, by analysis, tended to have less bulky disease, less amount of disease, and had received fewer prior therapies, so [they] were perhaps less resistant. That’s true in almost all our treatments. Those characteristics are true in any treatment that we do, so it’s not too surprising. [They] continued to be monitored long term.

Reference

Karimi YH, Vose JM, Clausen MR, et al. Novel analysis of 3-y results from the pivotal EPCORE NHL-1 study: Outcomes in patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL) and complete response (CR) at 2 y with epcoritamab (epcor) monotherapy. J Clin Oncol. 2025;43(suppl 16):7043. doi:10.1200/JCO.2025.43.16_suppl.7043