Background: BION-1301 is a first-in-class humanized antibody targeting a proliferation-inducing ligand (APRIL) that is currently being evaluated for the treatment of relapsed multiple myeloma (MM). APRIL binds to BCMA, thereby driving proliferation and survival of human MM cells. APRIL can also bind to TACI to promote MM cell survival (Tai et al., 2018). APRIL induces resistance to lenalidomide, bortezomib, and other standard-of-care drugs (Tai et al., 2016). BION-1301 blocks APRIL from binding to BCMA and TACI, leading to inhibition of MM cell proliferation and survival, and enhancement of MM sensitivity to other treatments (Tai et al., 2016). The objective of this Phase I/II first-in-human study is to determine the recommended phase 2 dose (RP2D) of BION-1301 by evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of BION-1301 administered as an intravenous (IV) infusion alone or with low dose dexamethasone (DEX).

Trial Design: This is an open-label, multicenter, first-in-human, 3+3 Phase I/II clinical study for subjects with relapsed or refractory MM whose disease has progressed after at least 3 prior systemic therapies. Phase I (Dose Escalation) dosing started as a 50 mg BION-1301 IV infusion. Dose escalation is to proceed in successive cohorts of subjects until the RP2D is identified. The maximum administered dose will not exceed 2700 mg. During initial dose escalation, the dosing interval is once every two weeks (Q2W) as a 2-hour infusion (3 hours for doses ≥2000 mg). Additional cohorts will be enrolled to evaluate weekly dosing for up to 8 weeks, followed by Q2W dosing with the same or a lower dose. Once an RP2D and schedule are identified, subjects will be randomized in the Phase II (Dose Confirmation) portion of the study to receive open-label BION-1301 alone or BION-1301 with low dose DEX at the assigned dose and schedule until disease progression or unacceptable toxicity. Phase I endpoints include incidence of dose-limiting toxicities, number and grade of treatment-emergent adverse events, PK/PD parameters, and relative reduction in serum and 24-hour urine M-protein levels defined as the maximum reduction from baseline; Phase II endpoints include objective response rate, progression-free survival, and overall survival. This study is designed to provide the RP2D of BION-1301 based on the totality of safety, tolerability, PK/PD, and clinical response data, and will inform future development of clinical studies for patients with MM.

Citation Format: Parameswaran Hari, Anastasios Raptis, James Berenson, Alexander Spira, Ajay Nooka, Maria Chaudhry, Nitya Nair, Hamid Namini, Jackie Walling, Deb Chapman, William Bensinger. Phase I/II safety and pharmacokinetics of BION-1301 targeting APRIL, a proliferation-inducing ligand, in adults with relapsed or refractory multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT107.