Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to Fcγriib, in Combination with Rituximab in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That Has Relapsed or Is Refractory to Rituximab

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1354-1354
• Main Authors: Karlsson, Ingrid, Gertsson, Susanne, Kilany, Suzanne, Borggren, Marie, Abrisqueta, Pau, Carneiro, Ana, Cordoba, Raul, Hagberg, Hans, Jerkeman, Mats, Mercadal, Santiago, Cohen, Jonathon B., Sancho, Juan-Manuel, Teige, Ingrid, Mårtensson, Linda, Frendéus, Björn, McAllister, Andres
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-147452

Introduction BI-1206 is a fully human anti-FcγRIIB antagonistic monoclonal antibody. BI-1206 enhances the activity of anti-CD20 antibodies such as rituximab by blocking the interaction of the anti-CD20 with this inhibitory receptor. This combination may overcome resistance to rituximab and enhance its activity. Methods The safety and tolerability profile of BI-1206 in combination with rituximab is currently investigated in the Phase 1/2a clinical trial 17-BI-1206-02. The study population includes subjects with follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) who have relapsed or are refractory to rituximab. Induction therapy consists of four weekly administrations of rituximab and three administrations of BI-1206, both given as i.v. infusions. In the first week of treatment rituximab is administered as single agent. In the following three weeks patients receive BI-1206 followed by rituximab. In Phase 1, a 3+3 study design is used, with escalating doses of BI-1206 and a fixed dose of rituximab (375 mg/m 2), with the aim of selecting the RP2D of BI-1206 for the expansion cohort (Phase 2a). Patients showing clinical benefit are eligible for continued maintenance therapy with dosing of BI-1206 and rituximab every 8 weeks for up to 7 cycles. The assessment of the pharmacokinetics (PK) of BI-1206 includes non-compartmental analysis (NCA), and the assessment of the pharmacodynamics (PD) includes B cell depletion, FcγRIIB expression and BI-1206 receptor occupancy (RO). Results With a cut-off date of July 20 th, 2021, 16 subjects have received doses of up to 100 mg BI-1206 in combination with rituximab (375 mg/m 2). Nine out of these received all four doses and were evaluated for therapeutic benefit. Three subjects were diagnosed with MCL, 1 with MZL and 12 with FL. The most frequent adverse advents (AEs) related to BI-1206 have been infusion related reactions (IRRs). These IRRs led to dose limiting toxicities (DLTs) in 4 subjects, 2 experienced G4 platelet drops, and 2 experienced G3 and G4 liver enzyme elevations. No signs of liver damage were observed, and all patients recovered within days of the event, leaving no sequelae. These events have been milder and less frequent after implementation of a novel pre-medication regimen. No DLTs have been observed after implementation of this regimen. Clinical responses were observed already at the starting dose (30 mg). To date three complete responses (CR) have been observed, one at