Evaluation of the Pharmacokinetics, Immunogenicity, and Safety of XmAb®2513 in the Ongoing Study XmAb2513-01: A Phase 1 Study of Every Other Week XmAb2513 to Evaluate the Safety, Tolerability, and Pharmacokinetics in Patients with Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma

XmAb2513 is a novel second-generation humanized monoclonal antibody (mAb) directed against the human cell surface antigen CD30, with an Fc region engineered to enhance cell killing activity via recruitment of effector cells through increased binding affinity to Fcγ receptors (FcγRs). The CD30 antigen (Ki-1) is a member of the tumor necrosis factor superfamily and was originally identified as a cell surface antigen on primary and cultured Reed-Sternberg cells of Hodgkin Lymphoma (HL). Expression of CD30 is a hallmark for the identification of HL and a subset of T-cell lymphomas, including Anaplastic Large Cell Lymphoma (ALCL). Preclinical in vitro data demonstrated XmAb2513 to be more potent with regards to antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP) than the first generation anti- CD30 antibodies MDX-060 and SGN-30. Studies in cynomolgus monkeys demonstrated that XmAb2513 exposure was proportional to dose with half-lives (t_½) ranging from 5 to 9 days in single dose studies and 12 to 17 days in repeat dose studies. The exposure and t_½ data from these cynomolgus monkey studies supported an every other week dosing interval in clinical trials. Based on these favorable features, a Phase 1 study has been initiated to examine the safety and efficacy of XmAb2513 in patients with relapsed and refractory classical HL and ALCL. This ongoing Phase 1 Study is currently evaluating every other week dosing of XmAb2513 using a dose-escalation study design to establish the maximum tolerated dose (MTD). The dose levels under evaluation are 0.3, 1.0, 3.0, 6.0, 9.0, and 12.0 mg/kg, given intravenously over two hours. To date, seven patients are enrolled on the study in the first three dose levels. Pre-study simulation of human exposure based on the pharmacokinetic (PK) parameters obtained from cynomolgus monkeys predicted that 0.3 mg/kg XmAb2513 in humans would result in serum trough levels of 1–1.5 μg/mL after four infusions given every other week. Interim PK and immunogenicity results from the treated patients have been analysed and the results observed thus far are on track with these simulations. Additionally, immunogenicity assessment for human anti-XmAb2513 (HAHA) showed that the treated patients are so far negative for HAHA. Importantly XmAb2513 was well tolerated. As dose escalation continues, results for human PK, immunogenicity, and safety for additional dose cohorts of HL patients, and preliminary safety and response assessment data will be presented.