A Phase 1 First-in-Human Monotherapy Study of F182112, a B-Cell Maturation Antigen (BCMA)-CD3 Bispecific Antibody, in Patients with Relapsed or Refractory Multiple Myeloma

作者：Mingyuan Sun, Junyuan Qi, Lugui Qiu, Jie Jin, Xin Li, Yongqiang Wei, Guimin Zhang, Xue Liu, Shaohong Yin · 发表于：Blood · 年份：2023 · DOI：10.1182/blood-2023-178948 · 被引用次数：5 · 研究领域：Multiple Myeloma Research and Treatments、Monoclonal and Polyclonal Antibodies Research、Nanoparticle-Based Drug Delivery

Introduction: Outcomes of relapsed or refractory Multiple Myeloma（RRMM） are generally poor after receiving current arsenal of therapies. Several novel kinds of drugs targeting BCMA are being developed to overcome resistance in this heavily treated patient population. F182112 is a BCMA x CD3 bispecific antibody that redirects CD3 + T cells to mediate T-cell activation and subsequently caused lysis of BCMA-expressing myeloma cells. A phase 1 clinical trial, NTP-F182112-001, has been launched to evaluate the safety and efficacy of F182112 in patients with RRMM. Shan Dong New Time Pharmaceutical Co. Ltd provides the funding support for the research. Clinical trial information: NCT04984434. Methods: This is a first-in-human, open-label, multicenter, phase 1 study. It has enrolled patients with RRMM who aged ≥ 18 years and previously received at least 2 prior lines of therapy including at least a proteasome inhibitor and an immunomodulatory agent. F182112 was administered intravenously once a week. First four dose cohorts of F182112 (0.01, 0.1, 0.3 and 1μg/kg) were planned for accelerated titration phase and the following four dose cohorts (3, 10, 20, and 30 μg/kg) were planned for i3+3 dose escalation phase . Primary objectives were to access safety and tolerability by monitoring adverse events (AEs) per CTCAE v5.0, with exception of CRS grading per ASTCT 2018. The target rate of dose-limiting toxicity (DLT) was 25% (equivalence interval± 5%). In addition, soluble BCMA, cytokines ...