KEY TAKEAWAYS
- The EPCORE™ NHL-1 trial evaluated the efficacy of single-agent epcoritamab in patients with R/R LBCL.
- Subcutaneous epcoritamab was administered to pts diagnosed with R/R CD20+ LBCL in 28-day cycles.
- The study demonstrated high CR and MRD-negativity rates with a manageable safety profile, and the outcomes support the ongoing phase 3 research investigating epcoritamab in various combinations and treatment lines.
For patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), effective treatments that provide deep, durable responses and long-term benefits are required. The EPCORE™ NHL-1 trial evaluated the efficacy of single-agent epcoritamab, an off-the-shelf, subcutaneous, CD3xCD20 T-cell–engaging bispecific antibody, in this population and demonstrated a high complete response (CR) and MRD-negativity rates with a manageable safety profile. The updated results, which include longer follow-ups, are presented in a challenging-to-treat population.
Subcutaneous epcoritamab was administered to pts diagnosed with R/R CD20+ LBCL in 28-day cycles. The dosage regimen consisted of step-up priming, intermediate, and 48-mg full doses. The administration frequency was once a week for cycles 1-3, once every two weeks for cycles 4-9, and once every four weeks for cycles ≥10 until either PD or unacceptable toxicity occurred.
As of November 18th, 2022, the study examined 157 LBCL pts (median age 64), including DLBCL (n=139; 12/88 double/triple-hit by FISH), HGBCL (n=9), PMBCL (n=4), and FL grade 3B (n=5). Among them, 36 pts are currently undergoing treatment (median 1.6 years from diagnosis to first dose), with a median of 3 (range, 2-11) prior treatment lines. The study found that 61% of pts had primary refractory disease, and 39% had prior CAR T; 75% progressed within six months of treatment. The LBCL overall response (63.1%) and CR (39.5%) rates were consistent across DLBCL (61.9% and 39.6%, respectively) with a 20-month median follow-up (range, 0.3+ to 28.2) and pts received an average of 9.1 cycles. The median duration of complete remission (CR) was 20.8 months. It took pts a median time of 2.7 months to achieve CR, with eight pts transitioning from partial response to CR after 36 weeks. Patients with LBCL had a median overall survival of 18.5 months (95% CI, 11.7-NR), while those with DLBCL had a median overall survival of 19.4 months (95% CI, 11.7-NR). Patients who achieved CR had a median overall survival of NR. Treatment-emergent adverse events (AEs) included CRS (51%), neutropenia (24%), pyrexia (24%), fatigue (23%), nausea (22%), and diarrhea (21%). Of the pts, 6% had G1-2 ICANS, and one had a G5 event with other factors. Treatment-emergent AEs resulted in 15 fatal cases, with two considered related (COVID-19, ICANS). CRS mainly occurred after the first full dose (cycle 1, day 15) and was primarily low grade (48% G1-2, 3% G3). One patient stopped treatment due to G1 CRS.
The findings report that administering epcoritamab through subcutaneous injection produces long-lasting complete responses with superior results and a manageable safety profile in individuals experiencing recurrent or refractory large B-cell lymphoma. Notably, no new safety signals were detected in this cohort. These exceptional outcomes support the ongoing phase 3 research investigating epcoritamab in various combinations and treatment lines.
Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_94
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03625037
Thieblemont, C., Karimi, Y., Jurczak, W., Cheah, C. Y., Clausen, M. R., Cunningham, D., Do, Y. R., Lewis, D. J., Gasiorowski, R., Kim, T. M., Poon, M. L., Feldman, T., Linton, K. M., Sureda, A., Hutchings, M., Cottereau, A., Tabaa, Y. A., Stirner, M. C., Liu, Y., . . . Ghesquieres, H. SUBCUTANEOUS EPCORITAMAB INDUCES DEEP, DURABLE COMPLETE REMISSIONS IN RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA: LONGER FOLLOW-UP FROM THE PIVOTAL EPCORE NHL-1 TRIAL. Hematological Oncology, 41, 142-144. https://doi.org/10.1002/hon.3163_94.
