At the 2023 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, Lorenzo Falchi, Memorial Sloan Kettering Cancer Center, New York, New York, presented updated EPCORE NHL-2 data from on the frontline treatment of patients with high-risk diffuse large B-cell lymphoma (DLBCL), including double-hit/triple-hit lymphoma, with epcoritamab combined R-CHOP.

Dr Falchi provided insights into arm 1 of the trial, which demonstrated promising results with strong and sustained efficacy. 

Transcript:

I'm Lorenzo Falchi. I'm an assistant attending in the Lymphoma Service at Memorial Sloan Kettering Cancer Center in New York City. And, here at ASCO, on behalf of my co-authors, I'm happy to share the results of our phase 1/2 study of epcoritamab combined with R-CHOP chemoimmunotherapy for the treatment of patients with diffuse large B-cell lymphoma at high risk.

This is a population of patients that represents an unmet need and, although curable, diffuse large B-cell lymphoma can be challenging, particularly the high-risk disease as defined by the [International Prognostic Index] (IPI) score, or for those patients with high grade B-cell lymphoma with MYC and BCL-2 or BCL-6 rearrangements. For these patients, unfortunately, we are looking at survival rates in the long-term that don't exceed 50% by a great measure, so there definitely exists an unmet need. 

Epcoritamab is a subcutaneously administered bispecific antibody that simultaneously binds CD-3 and CD-20, so it engages the endogenous immune cells to target and destroy lymphoma cells that express the protein CD-20, and diffuse large B-cell lymphoma cells universally express CD-20. So that's the rationale for the study. In a pivotal phase 2 study, epcoritamab as a single agent had demonstrated very promising preliminary results in terms of efficacy with responses observed in 60% of patients, complete response close to 40%. So, definitely very encouraging results there. 

As a single agent, epcoritamab had demonstrated very encouraging preliminary activity in a pivotal phase 1/2 study. We were all very excited to see that just a few weeks ago, epcoritamab became FDA-approved for the treatment of patients with recurrent diffuse large B-cell lymphoma and high-grade B-cell lymphoma after 2 or more lines of systemic therapy. The EPCORE NHL-2 study is a trial looking at the addition of epcoritamab to a number of standard-of-care therapies for patients with DLBCL or follicular lymphoma (FL). Arm 1 of this study tested the addition of epcoritamab to R-CHOP chemotherapy, as I mentioned previously. 

In this study, we have 47 patients and treatment included R-CHOP chemotherapy given per the standard of care, which means at the standard dose every 21 days for 6 cycles. Epcoritamab was administered from the start, that is cycle 1, day 1, and it was given on a step-up dose scheduled during cycle 1 and then weekly up until cycle 4. Then on day 1 of each cycle for cycles 5 and 6, and then every 4 weeks, to cover a total of a year of therapy.

Among these 47 patients, the distribution for gender was well-balanced. The median age was 66, and obviously all patients had an IPI score of 3 or above. Of note, about a quarter of our patient population was comprised of patients with double-hit or triple-hit lymphoma. About a third of the patients had an elevated LDH, so, I would say, the typical makeup of a patient population with high-risk DLBCL.

For this particular report, we have a follow-up of 14.2 months, so a relatively mature follow-up. In terms of safety, we didn't observe any new signal compared to previous reports of this study. In particular, CRS or cytokine release syndrome, was observed in about 60% of patients, but only 1 patient had a grade 3 event, meaning that the majority of patients had a mild to moderate CRS that did not require treatment in the intensive care unit, did not require higher level of care, and most cases were managed with either steroids alone, or in a few patients with the addition of tocilizumab.

The median time to onset of CRS was 2 days. The median time to resolution was also 2 days, and this CRS really resolved in all patients. We didn't really observe any significant degree of neurotoxicity in this study. The other common adverse events were cytopenias, which are expected in patients treated with R-CHOP chemotherapy, anemia, fatigue—all adverse events that are not necessarily attributable to epcoritamab alone.

When it comes to efficacy results, the treatment proved highly efficacious. The overall response rate was 100% and the complete response rate was 80% in the overall patient population. Interesting to note that patients with double or triple hit lymphoma also had an 82% complete response rate, which was very encouraging, but, generally speaking, the efficacy was preserved across risk categories.

We observed very deep responses across the board in our patient population, and, encouragingly, the depth of response was preserved in patients with double-or-triple-hit lymphoma. Also, interestingly, the few partial responses that we observed were also very deep from a tumor volume point of view. 

When we looked at durability of responses, we were also very much encouraged to see that the vast majority of patients who achieved the response and maintained that response within the available follow-up, specifically 95% of the patients who achieved a response, remained in a state of response at the time of this analysis. Even more encouraging was to observe that patients with double-or-triple-hit lymphoma didn't have a significantly different shape of their duration of response curve. 

In terms of duration of response, we were very encouraged to see that the chance of maintaining a response for those patients who achieved a response was very high. 95% of the patients who had a response remain in such state at the time of this analysis. And these figures were very similar for patients with double-or-triple-hit lymphomas. Again, a population of patients where we're used to seeing inferior results when treated with a simple R-CHOP chemotherapy.

Overall, we demonstrated that the combination of epcoritamab and R-CHOP is not only feasible, but it's also safely administered. The safety profile of the combination does not differ from the individual safety profiles of epcoritamab and the R-CHOP component. And, now, with a relatively mature follow up, we have seen a sustained efficacy of this combination. We think it's a promising initial result, and it certainly does warrant the ongoing exploration of this combination in a larger randomized phase 3 setting.

Source:

Falchi L, Clausen M, Offner F et al. Metabolic response rates of epcoritamab + R-CHOP in patients with previously untreated (1L) high-risk diffuse large B-cell lymphoma, including double-hit/triple-hit lymphoma: Updated EPCORE NHL-2 data. Presented at ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 7519.