Epcoritamab as Single Therapy for Relapsed/Refractory CLL/SLL

If BTK and BCL-2 inhibitors stop working, people with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) need additional treatment options. Although CAR T-cell therapy has emerged as an innovative approach, liso-cel achieves complete responses in less than 20% of cases, highlighting the urgent need for alternative strategies.

Epcoritamab (Epkinly, by Genmab and AbbVie) is a bispecific antibody and has shown potential as a single-agent therapy in early studies for relapsed/refractory CLL and Richter’s syndrome. At the press briefing of the 66th American Society of Hematology (ASH) conferences, Dr. Alexey Danilov presented the most recent findings from the EPCORE CLL-1 study. 

What is the EPCORE CLL-1 Study? 

The EPCORE CLL-1 study is a phase 1b/2 trial (still recruiting) that aims to review the safety and effectiveness of epcoritamab. If you would like to join the study to receive epcoritamab, click here.

It divides patients into two groups (cohorts):

• An expansion cohort: where epcoritamab is administered as an injection under the skin (subcutaneously) in 28-day cycles with varying frequencies over time.
• A cycle optimization cohort: consists of a modified step-up dosing regimen to address immune-related side effects such as cytokine release syndrome (CRS).

Both groups had received at least two prior treatments, including BTK inhibitors, and had CD20-positive CLL or small lymphocytic lymphoma (SLL) requiring treatment.

What Are the Results So Far? 

The results are based on a total of 40 patients and the study is still recruiting, however, there are relevant outcomes so far: 

• Efficacy Outcomes:

  • In the expansion cohort with 23 patients, the overall response rate (ORR) was 67%, and the complete response (CR) rate reached 39%. Median progression-free survival (PFS) was 12.8 months.
  • In the optimization cohort with 17 patients, the overall response rate was 60%, and the complete response was 10%.

• Safety and Toxicity:

  • In the expansion cohort, cytokine release syndrome (CRS) was common but manageable, with the majority being low-grade. Severe CRS occurred in 17% of cases, but no patients discontinued treatment due to these events.

  • Other side effects included fatigue, diarrhea, and injection-site reactions. Anemia and thrombocytopenia were frequent but often reflective of the underlying cancer.

  • No patients in the optimization cohort had life threatening adverse effects, on the expansion cohort, only four patients experienced that. 

Looking Ahead

The EPCORE CLL-1 study highlights epcoritamab as a new treatment option for patients with relapsed/refractory CLL/SLL who have received multiple prior treatments. Its ability to achieve durable responses, including complete remissions and deep reductions in disease burden, makes it a significant development for those with limited options. Furthermore, the adapted dosing strategy in the optimization cohort demonstrates meaningful improvements in safety.

These results encourage the continued exploration of epcoritamab in clinical trials, paving the way for its potential broader application in the treatment of CLL.

Stay Tuned!

If you want to remain updated with more CLL news, don't miss HealthTree's Conference Coverage section, where we'll feature all you need to know about CLL updates on treatments, patient-centered care, and more! 

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Sources: 

• Epcoritamab Monotherapy in Patients (Pts) with Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Results from CLL Expansion and Optimization Cohorts of Epcore CLL-1 by Alexey Danilov