Englumafusp Alfa (CD19-4-1BBL) Combined with Glofitamab Is Safe and Efficacious in Patients with r/r B-NHL: Extended Follow up Analysis of the Dose-Escalation Part of Phase 1 Trial BP41072

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.990-990
• Main Authors: Hutchings, Martin, Dickinson, Michael J., Gritti, Giuseppe, Carlo-Stella, Carmelo, Townsend, William, Bosch, Francesc, Bartlett, Nancy L., Cartron, Guillaume, Ghesquieres, Herve, Houot, Roch, Walter, Harriet S., Offner, Fritz, Dimier, Natalie, Jamois, Candice, Smith, Lance, Herter, Sylvia, Sahin, Denis, Keelara, Abiraj, Korfi, Koorosh, Gallien, Jeremy, Wasmer, Marie-Helene, Hinton, Heather, Whayman, Matt, Prieto, Isabel, Kazantzidis, Georgios, Lechner, Katharina, Morschhauser, Franck
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-200096

Background Englumafusp Alfa is a co-stimulatory antibody-like fusion protein targeting CD19 on B cells and 4-1BB on immune cells. Glofitamab single-agent has demonstrated efficacy in patients (pts) with relapsed/refractory B-cell Non-Hodgkin Lymphoma (r/r B-NHL) and is approved after at least two prior treatment lines. Preclinical in vivo models have confirmed that administering englumafusp Alfa in combination with glofitamab enhances, prolongs, and deepens anti-tumor activity (C. Claus et al., 2019). We present PFS, OS, DoR and extended follow-up data of the final dose escalation of BP41072 (NCT04077723), a phase 1b study combining englumafusp alfa with glofitamab in pts with r/r B-NHL. Methods Pts with r/r B-NHL after at least one prior treatment, ECOG 0-1, received glofitamab step up dosing (2.5/10/30mg) after a single obinutuzumab dose (1000mg). One week after (i.e. cycle 2 day 8), pts received englumafusp alfa and from C3D1 onwards both agents were given the same day Q3W. Therapy was administered intravenously for a maximum of 12 cycles. Dose escalation was conducted using a mCRM EWOC model. Complete response rates (CRR) and best overall response rates (BORR) were assessed using Lugano criteria. Results As of the Clinical cut-off date on June 3, 2024, 134 pts were enrolled. Among them, 83 pts had aggressive NHL (aNHL), including 44 DLBCL, 16 HGBL-DH/TH, 18 trFL, 3 transformed other indolent NHL and 2 FL grade 3B. Additionally, 24 pts had indolent disease (iNHL), comprising 23 FL and 1 MZL. Englumafusp alfa doses ranged from 0.36 up to 75mg without reaching a maximum tolerated dose level. Pts (aNHL/iNHL) had median age 63/64, 41%/42% were female, 98%/88% were white, 65%/79% were not Hispanic or Latino, 14%/0 were Hispanic or Latino, 47%/29% presented with ECOG 1, and 52%/54% had stage IV disease. Both patient groups had a median of 3 prior treatment lines (range 1-8/6), 19%/8% were primary refractory, and 49%/4% had received prior CAR-T cell therapy. Patients received a median of 8.5 treatment cycles (1-12). Across the 134 safety-evaluable pts (all histologies), the most common adverse events were cytokine release syndrome (CRS, 55.2%), anemia (32.1%), COVID-19 (29.9%), and neutropenia (27.6%). Grade 5 events were reported in 9 (6.7%) pts and were related to study treatments in 3 patients (pleurisy, organising pneumonia and pneumocystis jirovecci pneumonia). The latter event qualified as a dose-limiting toxicity (n=1). CRS was mostly confined to the fi