Subcutaneous Epcoritamab With Rituximab and Lenalidomide for Relapsed/Refractory Follicular Lymphoma

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Lorenzo Falchi, MD, Memorial Sloan Kettering Cancer Center, New York, NY, presents updated findings from a phase 1/2 trial exploring subcutaneous epcoritamab combined with rituximab and lenalidomide treatment for patients with relapsed/refractory follicular lymphoma. The abstract was awarded Best Lymphoma Abstract at the Congress.

Transcript:

Hello, I'm Dr Lorenzo Falchi and I'm a lymphoma specialist at Memorial Sloan Kettering Cancer Center in New York City. Here at the 2022 Lymphoma, Leukemia & Myeloma Congress, we were very happy to share the results of our multicenter global phase 1/2 trial of combined epcoritamab and rituximab and lenalidomide for the treatment of patients with relapsed or refractory follicular lymphoma. This was a multicenter effort, so I'm happy to share these results on behalf of all my coauthors.

The study was born from the consideration that advanced follicular lymphoma, particularly relapsed or refractory follicular lymphoma, does remain an incurable illness, and the quality and depth of responses to the subsequent therapies tend to be lower and of shorter duration. Novel treatments are certainly welcome and needed in this space and epcoritamab does just that.

Epcoritamab is a subcutaneously administered bispecific antibody that simultaneously binds CD3 on the T cells and CD20 on the B cells and induces T-cell mediated killing of the target CD20-positive malignant cells. In a previous international phase 1/2 trial named EpcorNHL1, this drug had really shown very promising results in patients with heavily pretreated B-cell non-Hodgkin lymphoma and that includes follicular lymphoma.

Because the mechanism of action of epcoritamab is distinct as is its toxicity profile compared to the R² backbone therapy, obviously the combination lent itself to be tested in this setting. And the study EpcorNHL2 is a study evaluating epcoritamab with a number of different standard of care options in patients with large cell or follicular lymphoma. What we presented at the meeting were the results of arm 2, which looked at epcoritamab in combination with R² in this particular patient population. The study had a small dose escalation portion where 2 doses of epcoritamab were tested eventually to 48 mg.

The study was a phase 1/2 design. It tested 2 doses of epcoritamab at 24 and 48 mg. Eventually 48 mg was chosen as a recommended phase 2 dose. In the dose-expansion portion of the study, there were 2 subcohorts: cohort 2A testing a little bit more of an intense dose of epcoritamab and cohort 2B with a less intense schedule. The R² portion was administered per the augment trial and obviously the objectives of the study were to evaluate safety and tolerability in the escalation and then responses in the dose-expansion cohort.

At the time of this presentation, we had a follow up of 8.6 months. We had 30 patients in arm 2A and 44 in arm 2B. There were a few key differences between the two, particularly arm 2B patients were a little bit enriched in cases of follicular lymphoma grade 3A. Also, in this population, the median time from the last line of therapy to study entry was a little bit shorter, overall suggesting that the population in arm 2B was a little bit more difficult to treat, more refractory, than the one in 2A.

However, most of the results I shared were regarding arm 2A. And in that sense, at the time the data cut off, most of the patients were still on therapy in that cohort and only less than 50% of patients had generally contained dose delays due to treatment emergent adverse events. Some of those adverse events were actually intercurrent COVID-19 illness.

In terms of safety, we really didn't observe concerning or new signals. The toxicity profiles of epcoritamab and R² didn't overlap almost at all, with the exception of neutropenia, which could be compounded by both treatment components. In terms of adverse events of special interest, epcoritamab was associated with injection site reactions and CRS or cytokine release syndrome in about 50% of the patients from each.

Zooming in a little bit more on the CRS, which is obviously an adverse event of particular interest, half of the patients had at least 1 event, but only 2 patients had a grade 3 event, which means CRS severe enough to be hospitalized, require pressure support. All these CRS events resolved. They occurred after a median of a couple of days and resolved in a median of 4 days from the time of onset. Most of these events occurred at cycle 1, day 15, which is when the first full dose of epcoritamab was administered.

Now in terms of efficacy, and again focusing on arm 2A where the data more mature, all of the 28 invaluable patients had an objective response and all but 1 patient had a complete response, which was very gratifying. For a fair comparison between arm 2A and 2B, we looked at a snapshot of 6 weeks and at that point the overall and complete response rates were super imposable with 90% and 60 to 70% respectively. And then looking at the dynamics of response, most of the patients who had a response had a complete response at the first assessment.

The time of onset of response was very quick, and the majority of patients who had a PR or a partial response at first assessment subsequently converted that to a complete response. The responses were durable, even though the follow up, again, as I mentioned very short, but particularly for arm 2A, where the follow up is a little bit more mature, only 2 patients lost their response at a follow up of 8 to 9 months.

I think we were very pleased to see that the combination of epcoritamab and R² was very active in patients with relapsed [or refractory] follicular lymphoma, including those who are more difficult to treat, such as the refractory patients and those who have been treated with a high number of prior lines of therapy. The 2 components of this triplet regiment were combinable with no real new safety signals, nothing that we haven't seen with either a single agent.

I think collectively efficacy and safety data for R² epcoritamab in this preliminary analysis suggests and support further exploration of the triplet. And this is being done and we hope to be presenting updates of this exciting study soon in our coming meetings.

Source:

Falchi, L. Presentation of Best Lymphoma Abstract: Subcutaneous Epcoritamab Combined With Rituximab + Lenalidomide for the Treatment of Patients With Relapsed or Refractory Follicular Lymphoma: Phase 1/2 Trial Update. Presented at Leukemia, Lymphoma & Myeloma Congress; October 18-22, 2022; New York, NY.