INTRODUCTION: CAR T is approved in the relapsed/refractory (R/R) LBCL. Patients (pts) with R/R LBCL who progressed after CAR T therapy have poor prognoses. Epcor, a CD3×CD20 bispecific antibody approved in 3L+ LBCL, showed deep, durable responses with a manageable safety profile in the pivotal phase 2 EPCORE NHL-1 trial (NCT03625037) in pts with R/R LBCL, including those with challenging-to-treat disease. Previous reports have shown that epcor is effective in CAR T-naïve populations in the NHL-1 trial (Karimi, YH et al. ASH 2024), and we report efficacy and safety results from a subanalysis of LBCL pts with previous CAR T exposure from the 3-year follow-up.

METHODS: Adults with R/R CD20+ LBCL received subcutaneous epcor in 28-day cycles (C; once weekly (QW) step-up doses in weeks 1–3 of C1, then full doses QW through C3, Q2W in C4–9, and Q4W in C10 and thereafter) until disease progression or unacceptable toxicity. The primary endpoint is overall response rate (ORR) per Lugano criteria. Efficacy results presented here are based on investigators' assessment. Additional endpoints reported here are complete response (CR), duration of complete response (DOCR), overall survival (OS), progression-free survival (PFS), and safety. Patients were analyzed based on time to progression since prior CAR T therapy.

RESULTS: As of 03 May 2024, 61 pts with LBCL (53 diffuse LBCL [DLBCL] 58 DLBCL plus high-grade BCL [HGBCL]) progressed ≤3 months (mo; n=31), >3 to ≤6 mo (n=12), or ≥6 mo (n=18) after CAR T in a prior line of treatment (LOT). Most pts who received epcor after prior CAR T progressed ≤3 mo after receiving CAR T (n=31). Most pts were heavily pretreated, with median prior LOT of 4 (range: 3–8) for pts who progressed ≤3 mo, 3 (range: 3–6) for >3 to ≤6 mo, and 4 (range: 2–11) for >6 mo. The vast majority of pts who progressed after prior CAR T were also primary refractory in their front-line therapy (83.9% for ≤3 mo, 91.7% for >3 to ≤6 mo, 66.7% for >6 mo). ORR was 41.9% (95% CI: 24.5%, 60.9%; CR, 22.6%) for pts that progressed ≤3 mo after prior CAR T, 58.3% (95% CI: 27.7%, 84.8%; CR, 50.0%) for >3 to ≤6 mo, and 50.0% (95% CI: 26.0%, 74.0%; CR, 50.0%) for >6 mo. Median DOCR was not reached (NR) across all subgroups. Median OS was 7.3 mo (95% CI: 4.1, 32.5) for pts that progressed ≤3 mo after prior CAR T, NR for >3 to ≤6 mo, and 23.7 mo (95% CI: 11.7, NR) for >6 mo. Median PFS was 1.4 mo (95% CI: 1.2, 4.1) for pts that progressed ≤3 mo after prior CAR T, NR for >3 to ≤6 mo, and 11.0 mo (95% CI: 2.7, NR) for >6 mo. The safety profile was consistent with earlier NHL-1 study data. CRS events were mostly low grade (G) and occurred in 36.1% of CAR T-exposed LBCL pts (G1, 29.5%; G2, 4.9%; G3, 1.6%); median time to first CRS onset from initiation was 15.5 days (range, 1–31), median time to resolution was 2 days (range, 1–8), and all resolved. G≥2 CRS events were observed at lower rates for DLBCL pts with prior CAR T vs without prior CAR T for pts from the EPCORE NHL-1 and EPCORE NHL-3 trials (Putnins M, et al. AACR 2025), and the CRS rates reported here were lower than those reported for the ITT population of the EPCORE NHL-1 study (51%; 32% G1, 16% G2, 3% G3; Vose JM, et al. ASH 2024). ICANS events were mostly low grade and occurred in 4.9% of pts (G1, 1.6%; G2, 3.3%); median time to first ICANS onset was 17 days (range, 7–22); all resolved with median time to resolution 6 days (range, 1–9). G≥3 treatment-emergent adverse events were reported in 41 (67.2%) pts. Results will also be reported for pts who received CAR T as their most recent LOT prior to receiving epcor. Data for the overall population was presented previously (Vose JM, et al. ASH 2024).

CONCLUSION: Epcor demonstrated deep and durable responses regardless of prior therapy. While potentially greater benefit for pts with prior CAR T ≥3 mo was observed, clinically meaningful activity was seen across all pt groups. The majority of CAR T-exposed pts were heavily pretreated (median prior LOT of 4) and primary refractory to CAR T in the NHL-1 study. CRS and ICANS events were predominantly low grade, with a lower incidence of CRS observed in post-CAR T patients compared to the broader NHL-1 population. These findings reinforce the potential of epcor to deliver deep and durable responses across a range of pt profiles, including those with heavily treated and highly refractory disease, underscoring its role as a versatile and effective option in R/R LBCL.

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2025
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