Background: While high-dose therapy (HDT)–autologous stem cell transplant (ASCT) is potentially curative for pts with R/R DLBCL, many do not receive this treatment (tx) due to insufficient response to salvage chemoimmunotherapy; better options are needed. Epcoritamab is a CD3xCD20 bispecific antibody with efficacy and safety in R/R DLBCL as a single agent and in combination. We report updated data from epcoritamab in combination with rituximab, dexamethasone, cytarabine, and oxaliplatin or carboplatin (R-DHAX/C) in pts with R/R DLBCL eligible for HDT-ASCT, including high-risk pts (progressed within 12 mo of initial tx or primary refractory), from EPCORE™ NHL-2 (phase 1/2; NCT04663347). Methods: Adults with R/R CD20⁺ DLBCL eligible for HDT-ASCT received R-DHAX/C and epcoritamab (2 step-up doses, then 24- or 48-mg full doses) in 21-d cycles (Cs): QW, C1–3. If HDT-ASCT was deferred, pts could continue epcoritamab (21-d C: QW, C4; 28-d Cs: Q2W, C5–9; Q4W, C≥10) until disease progression. Primary endpoint was overall response rate (ORR; Lugano criteria). Results: As of Dec 15, 2023, 29 pts (median age, 58 y) received epcoritamab (24 mg, n=3; 48 mg, n=26) + R-DHAX/C. At baseline, 24 pts (83%) had progressed within 12 mo of initial tx, 19 (66%) had primary refractory disease (no response or relapse within 6 mo of initial tx), and 3 (10%) had prior CAR T. At 27.5 mo median follow-up, 16 (55%) pts had proceeded to HDT-ASCT and 2 (7%) remained on tx. ORR was 76% and complete response (CR) rate was 69% (Table). Median time to response was 1.4 mo (CR, 1.5 mo). At 24 mo, per Kaplan–Meier estimates, 60% of pts remained progression free, while 90% of pts who proceeded to ASCT (n=16) and 60% of pts who continued epcoritamab without ASCT (n=5) remained progression free; additionally, 90% of pts with CR who received ASCT (n=15) and 100% of high-risk pts with CR who received ASCT (n=12) remained in response. An estimated 86% of pts remained alive at 24 mo. The most common tx-emergent AEs (TEAEs) of any grade (G) were thrombocytopenia (76%), anemia (59%), nausea (48%), and neutropenia (48%; febrile neutropenia, 17%). CRS was low grade (38% G1, 7% G2), resolved, and did not lead to tx discontinuation. ICANS (G2) occurred in 1 pt and led to tx discontinuation. There were no fatal TEAEs. Conclusions: Longer follow-up reaffirms the efficacy and feasibility of epcoritamab + R-DHAX/C in ASCT-eligible DLBCL. Response rates were high and most pts proceeded to ASCT. Safety was manageable and consistent with prior data. These results, including new high-risk subgroup analyses, support future evaluation of epcoritamab + R-DHAX/C in ASCT-eligible DLBCL. Clinical trial information: NCT04663347.

^aFor primary refractory subset (n=19), ORR/CR rates were 68%/58%.

^bKaplan–Meier estimate.