Epkinly monotherapy demonstrated deep responses and a positive security profile in sufferers with closely pretreated persistent lymphocytic leukemia.
Closely pretreated sufferers with persistent lymphocytic leukemia (CLL) confirmed deep responses when handled with Epkinly (epcoritamab-bysp) monotherapy, in line with findings from the EPCORE CLL-1 trial, introduced in a press briefing throughout the 2024 ASH Annual Assembly.
Outcomes confirmed that within the enlargement cohort, which had a median follow-up of twenty-two.8 months, the general response fee (ORR) in 21 response-evaluable sufferers was 67%, and the entire response (CR) fee was 43%. In 15 sufferers with TP53 aberrations, these charges have been 67% and 33%, respectively; within the IGHV-unmutated group of 16 sufferers, these have been 63% and 44%. In 19 sufferers who have been double-exposed to each a BTK and BCL-2 inhibitor, the ORR was 53% and the CR fee was 37%.
Within the cycle 1 optimization (C1 OPT) cohort, which had a median follow-up of two.9 months amongst 10 evaluable sufferers, the ORR was 60%, and the CR fee was 10%.
“There was a comparable ORR between the enlargement and C1 OPT cohorts, with restricted follow-up for C1 OPT efficacy,” defined lead research writer Dr. Alexey Danilov, in a press briefing throughout the assembly. “Easy C1 OPT measures of a further [step-up dosing], dexamethasone, and satisfactory hydration decreased the chance and severity of [side effects] of particular curiosity.”
Danilov serves because the Marianne and Gerhard Pinkus Professor of Early Medical Therapeutics, medical director of the Early Section Therapeutics Program for the Programs Medical Trials Workplace, co-director of the Toni Stephenson Lymphoma Middle, and professor within the Division of Lymphoma of the Division of Hematology & Hematopoietic Cell Transplantation, all inside Metropolis of Hope in Duarte, California.
Glossary:
General response fee (ORR): the proportion of sufferers who’ve a whole or partial response to therapy, that means their tumors both disappeared or shrunk after therapy.
Full response (CR): sufferers who absolutely responded to therapy, that means they not have indicators or signs of most cancers.
Cytokine launch syndrome (CRS): a situation that happens when the physique overreacts to immunotherapy, which may grow to be life-threatening if not handled instantly.
ECOG efficiency standing: a measurement of how independently sufferers can carry out day by day duties. A standing of zero means they’ll full duties independently and a standing of 4 means they can not carry out duties independently.
Immune effector cell-associated neurotoxicity syndrome (ICANS): a aspect impact of immunotherapies; the physique’s response that may trigger irritation within the mind.
Medical tumor lysis syndrome (CTLS): a situation that may be life-threatening, by which most cancers cells quickly break down and launch their contents into the bloodstream, resulting in issues.
Minimal residual illness (MRD): microscopic traces of most cancers cells that stay within the physique after therapy.
Partial response (PR): sufferers whose tumors shrunk however didn’t utterly disappear after therapy.
Secure illness (SD): sufferers whose most cancers didn’t worsen or enhance after therapy.
Progressive illness (PD): sufferers whose most cancers worsened or unfold after therapy.
Development-free survival (PFS): time after therapy when sufferers dwell with out their illness worsening or spreading.
General survival (OS): time sufferers dwell, no matter their illness standing, till dying of any trigger.
Epkinly is a bispecific CD20-directed CD3 T-cell engager, which was FDA-approved in June for the therapy of grownup sufferers with relapsed or refractory follicular lymphoma following at the very least two prior traces of systemic remedy.
Within the enlargement cohort of the Epcore CLL-1 trial, 23 sufferers got a step-up dose schedule of 0.16 milligrams (mg) of Epkinly on cycle 1, day 1; 0.8 mg on cycle 1, day 8; after which the primary full dose of 48 mg on cycle 1, day 15. Prophylaxis for cytokine launch syndrome (CRS) with prednisone was additionally permitted. The info cutoff date was Could 28, 2024, and the median follow-up was 22.8 months.
Within the C1 OPT cohort of 17 sufferers, CRS prophylaxis with dexamethasone and satisfactory hydration was given. This additionally included a step-up dose design of 0.16 mg on cycle 1, day 1; 0.8 mg on cycle 1, day 8; 3 mg on cycle 1, day 15; adopted by the primary full dose of 48 mg on cycle 1, day 22. Right here, the info cutoff date was Could 28, 2024, and the median follow-up was 2.9 months.
To be eligible for enrollment, sufferers should have had CD20-positive relapsed or refractory CLL, acquired at the very least two prior traces of systemic remedy and had an ECOG efficiency standing of 0 to 2. No prior allogeneic hematopoietic cell transplant was permitted.
The first finish level within the enlargement cohort was ORR; within the C1 OPT cohort, this was incidence and severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and medical tumor lysis syndrome (CTLS). Key secondary finish factors within the enlargement cohort included CR fee, time to response, minimal residual illness (MRD), and security and tolerability.
Within the enlargement and C1 OPT cohorts, respectively, the median age was 72 years and 68 years; 74% and 82% of sufferers have been male. The median time from preliminary analysis to first dose was 13 and 11 years, respectively. The median variety of prior traces of remedy was 4 in each therapy teams; 61% and 53% acquired at the very least 4 prior traces of remedy. The median time from the final therapy to the primary dose was 0.7 months and 1.6 months, respectively. All sufferers in each teams beforehand acquired a BTK inhibitor; 83% and 88% of sufferers had acquired a BCL-2 inhibitor.
Additional efficacy findings confirmed that, within the response-evaluable group of the enlargement cohort, the partial response (PR) fee was 24%, the secure illness (SD) fee was 19%, and 5% of sufferers had progressive illness (PD). In these with TP53 aberrations, these charges have been 33%, 13%, and seven%. In sufferers with IGHV-unmutated illness, the charges have been 19%, 19%, and 0%, respectively. Within the double-exposed subgroup, these charges have been 16%, 21%, and 5%, respectively.
Within the C1 OPT cohort, the PR, SD, and PD charges have been 50%, 20%, and 10%, respectively.
Within the enlargement cohort, the median time to response was two months, and the median time to CR was 5.6 months. The estimated one-year progression-free survival (PFS) and general survival (OS) charges have been 52% and 70%, respectively. The median PFS was 12.8 months, and the median OS was not reached. When an OS shouldn’t be reached, it means the typical quantity of sufferers didn’t die on the time of information assortment.
Danilov famous that, within the C1 OPT cohort, the speed and severity of CRS have been decreased, and there have been no circumstances of ICANS or CTLS. Right here, the general CRS fee was 82% and was grade 1 (delicate), 2 (severe) and three in 71%, 12%, and 0% of sufferers. Within the enlargement cohort, the CRS fee was 96% and was grade 1, 2, and three in 9%, 70% and 17% of sufferers, respectively.
Actemra (tocilizumab; a therapy for CRS) was given in 91% and 43% of sufferers within the enlargement and C1 OPT cohorts, respectively. No such occasions led to therapy discontinuation, and all CRS circumstances have been resolved in each cohorts. The median time to decision was three days within the enlargement cohort and three.5 days within the C1 OPT cohort.
Within the enlargement cohort, ICANS occurred in 13% of sufferers and have been both grade 1 (4%) or 2 (9%); there was one case of CTLS, which was grade 2.
CRS occasions have been additionally evaluated by dosing interval. Within the enlargement cohort, these occurred on the first step-up dose (grade 1, 13%; grade 2, 21.7%), second step-up dose (grade 1, 36.4%; grade 2 13.6%), first full dose (grade 1, 18.2%; grade 2, 63.6%; grade 3, 18.2%); second full dose (grade 1, 10.5%; grade 2, 21.1%) and third full dose (grade 1, 6.3%; grade 2, 18.8%).
Within the C1 OPT cohort, these additionally occurred on the first step-up dose (grade 1, 23.5%), second step-up dose (grade 1, 12.5%; grade 2, 6.3%), third step-up dose (grade 1, 31.3%), first full dose (grade 1, 46.7%; grade 2, 13.3%) second full dose (grade 1, 30.8%; grade 2, 7.7%) and third full dose (33.3%).
The section 1/2 EPCORE CLL-1 trial is evaluating single-agent Epkinly and as a mixture routine with numerous brokers in sufferers with CLL and Richter’s transformation. It’s at the moment recruiting sufferers.
Reference:
“Epcoritamab monotherapy in sufferers (Pts) with relapsed or refractory (R/R) persistent lymphocytic leukemia (CLL): outcomes from CLL enlargement and optimization cohorts of Epcore CLL-1” by Dr. Alexey Danilov, et al. Offered at: 2024 ASH Annual Assembly & Exposition; December 7-10, 2024; San Diego, CA. Summary 883.
For extra information on most cancers updates, analysis and schooling, don’t overlook to subscribe to CURE®’s newsletters right here.
