Epcoritamab (epco) with gemcitabine + oxaliplatin (GemOx) in patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) induces high response rate even in pts failing CAR T therapy.

Abstract

7527 Background: Pts with R/R DLBCL who fail or are ineligible for ASCT have very poor outcomes with standard palliative chemotherapy. Rituximab + GemOx had a complete response rate of 33% (Cazelles et al, Leuk Lymphoma 2021); novel approaches are needed. Epco is a subcutaneously administered bispecific antibody targeting CD3 on T cells and CD20 on B cells. In the EPCORE NHL-1 dose-escalation trial, epco had manageable safety and antitumor activity in heavily pretreated B-cell NHL including DLBCL. EPCORE NHL-2 is a phase 1/2 trial evaluating epco + standard B-cell NHL therapies; shown here are results from arm 5 (NCT04663347). Methods: Adults with R/R CD20+ DLBCL who failed or were ineligible for ASCT received epco (QW, cycle [C] 1–3; Q2W, C4–9; Q4W, C≥10) and GemOx (Q2W, C1–4) until disease progression or unacceptable toxicity (28 d/C). Step-up epco dosing and prophylactic corticosteroids were required in C1 to mitigate CRS. Response was assessed by PET-CT per Lugano 2014 criteria. Results: As of Dec 1, 2021, 27 pts (median age, 71 y; range, 47–87 y) had received epco + GemOx (epco 24 mg, n=3; 48 mg, n=24). Most were stage IV (56%), primary refractory (56%), and refractory to last therapy (70%). Median number of prior therapies was 2 (range, 1–13). Median follow-up was 6.0 mo (range, 1.0–11.1), with treatment (Tx) ongoing in 16 pts (59%). The most common Tx-emergent AEs were CRS (70%), thrombocytopenia (70%), neutropenia (56%), anemia (52%), and infections (52%). CRS events were all grade (G) 1/2, with most cases occurring in C1; all cases resolved. One pt had ICANS (G3); 1 pt had tumor lysis syndrome (G3). Six pts (22%) had G5 AEs; investigator could not rule out contribution of epco in 2 pts: small bowel perforation in pt (72 y) with transformed DLBCL and extensive gastrointestinal involvement (had complete metabolic response [CMR]); acute hepatitis/multiorgan failure in pt (68 y) with transformed DLBCL and liver involvement (had CMR). Of 4 pts with fatal AEs unrelated to epcoritamab by investigator, 2 (87 y) had primary refractory disease and 2 (74 y) had multiple comorbidities. Response is shown in the Table. At the time of data cut, 65% of responders remained in response with the longest duration of response 6.9 mo. All 3 pts with prior CAR T remained on Tx and in response (2 CMR and 1 partial metabolic response [PMR]). Conclusions: When considering individual safety profiles of epco or GemOx, no unexpected safety findings were observed for epco + GemOx. In this R/R population with high unmet need, these initial data are encouraging and warrant further clinical evaluation. Clinical trial information: NCT04663347. [Table: see text]