PHASE 1/2A CLINICAL TRIAL OF BI‐1206, A MONOCLONAL ANTIBODY TO CD32B (FCGRIIB), IN COMBINATION WITH RITUXIMAB IN SUBJECTS WITH INDOLENT B‐CELL LYMPHOMA

Abstract

Introduction: Anti-CD20 antibodies, such as rituximab, are an essential therapy resource in patients with B-cell lymphomas. However, approximately 15% of patients are refractory to treatment, and 25% relapse within 3 years following treatment. Non-clinical and retrospective clinical data indicate that the inhibitory Fc receptor CD32b promotes resistance through mechanisms acting on tumor and immune effector cells. Expressed on tumor B cells, CD32b triggers rituximab internalization, and tumor CD32b expression correlates inversely with response to rituximab or rituximab-containing therapy in MCL, FL, and DLBCL. BI-1206 is a human recombinant anti-CD32b (FcγRIIB) antagonistic IgG1 antibody that blocks rituximab internalization and, in non-clinical experimental models, enhances efficacy and overcomes rituximab resistance. During early clinical development of BI-1206, frequent infusion-related reactions were observed after intravenous (IV) administration. The development of a novel pre-medication regimen using two doses (16–24 h and 1 h) of corticosteroids prior to IV administration, as well as of a subcutaneous (SC) administration, have been shown to improve the tolerability of BI-1206 significantly, and both methods of administration are evaluated in the current trial. Methods: The current phase 1/2a multicenter clinical trial includes relapsed or refractory B-cell lymphoma, including FL (except FL grade 3B), MZL, and MCL. This trial will evaluate the safety and tolerability of IV and SC BI-1206 administered in combination with rituximab. The ivRP2D has been established, and enrollment of patients to SC BI-1206 to establish scRP2D has started. Ph2a of the trial will consist of cohorts of at minimum 6 and maximum 12 subjects each, receiving ivRP2D, scRP2D, and potential additional dose levels of interest. During induction therapy, patients receive one dose of single-agent rituximab (375 mg/m2) followed by dosing of BI-1206 with subsequent rituximab on weeks 2, 3, and 4. Patients showing clinical benefit (complete response [CR], partial response [PR], or stable disease [SD]) at week 6 are eligible for continued maintenance therapy with dosing of BI-1206 and rituximab every 8 weeks for up to 7 cycles. The research was funded by: BioInvent Keywords: Combination Therapies, Immunotherapy, Ongoing Trials Conflicts of interests pertinent to the abstract. M. Jerkeman Honoraria: Gilead, Janssen, Roche, AstraZeneca, Abbvie, BMS Research funding: Gilead, Janssen, Roche, AstraZeneca, Abbvie, BMS P. Abrisqueta Costa Consultant or advisory role Janssen, Roche, Abbvie, BMS, Astrazeneca, Gilead, Beigene Honoraria: Janssen, Roche, Abbvie, BMS, Astrazeneca, Gilead Educational grants: Janssen, Abbvie J. M. Sancho Cia Consultant or advisory role Roche, Janssen, Novartis, BMS-Celgene, Kite-Gilead, Beigene, Lilly, Incyte, Miltenyi Biomedicine Honoraria: Roche, Janssen, Novartis, BMS-Celgene, Kite-Gilead, Takeda, Incyte M. Bastos-Oreiro Consultant or advisory role Roche, Kite, Novartis, Takeda, Janssen, Incyte Honoraria: Roche, Kite, Novartis, Takeda, Janssen, Incyte Research funding: Roche Educational grants: Roche, Kite, Novartis, Takeda, Janssen, Incyte J. B. Cohen Consultant or advisory role Janssen, Astra Zeneca, BeiGene, Loxo/Lilly, Gilead, ADCT Research funding: Genentech, Takeda, Novartis, Celgene, BioInvent, LAM Therapeutics, Loxo/Lilly, Astra Zeneca R. Cordoba Mascunano Consultant or advisory role Roche, Abbvie, Janssen, Astra Zeneca, Beigene, Lilly, Kite, Incyte, Takeda, Kiowa-Kirin E. Domingo Domenech Consultant or advisory role TAKEDA Honoraria: TAKEDA Educational grants: TAKEDA, BMS S. Novelli Canales Honoraria: Mundipharma Research funding: Novartis M. Borggren Employment or leadership position: BioInvent Stock ownership: BioInvent B. Frendeus Employment or leadership position: BioInvent Stock ownership: BioInvent I. Karlsson Employment or leadership position: BioInvent Stock ownership: BioInvent L. Mårtensson Employment or leadership position: BioInvent Stock ownership: BioInvent S. Patel Employment or leadership position: BioInvent Stock ownership: BioInvent I. Teige Employment or leadership position: BioInvent Stock ownership: BioInvent J. E. Wallin Employment or leadership position: BioInvent, Lilly Keywords: combination therapies, immunotherapy, ongoing trials Stock ownership: BioInvent, Lilly A. Mc Allister Employment or leadership position: BioInvent Stock ownership: BioInvent