Date: 2017-12-18
Type of
information: Treatment of the first patient
phase: 1-2
Announcement: treatment of the first patient
Company: Aduro Biotech (USA - CA)
Product: BION-1301
Action
mechanism:
- monoclonal antibody. APRIL (A PRoliferation-Inducing Ligand) is a member of the tumor necrosis factor (TNF) superfamily and is primarily secreted by bone marrow and/or myeloid cells. APRIL is overproduced in patients with multiple myeloma and binds to BCMA (B cell maturation antigen) and TACI (Transmembrane Activator and CAML Interactor) to stimulate a wide variety of responses that promote multiple myeloma growth and suppress the immune system so that the tumor cells are allowed to proliferate. BION-1301 is a humanized anti-APRIL antibody that has been shown in preclinical studies to effectively neutralize APRIL, eliminate malignant cells and reduce resistance to therapy in models of multiple myeloma. In addition to multiple myeloma, APRIL’s role in other cancers and in B cell dependent autoimmune and inflammatory diseases indicate that BION-1301 may also be useful in treating chronic lymphocytic leukemia, colorectal cancer and Berger’s disease (caused by IgA antibody deposits in the kidneys).
- Recently, two datasets on anti-APRIL were presented at the 59th American Society of Hematology (ASH) Annual Meeting. Data presented by Yu-Tzu Tai, Ph.D., of the Dana Farber Cancer Institute demonstrate that BION-1301 and its parental antibody blocked APRIL binding to both its receptors BCMA and TACI. Blocking APRIL with BION-1301 (or its parental antibody) not only inhibited proliferation and survival of multiple myeloma cells but it also alleviated drug resistance and immune suppression in preclinical models and cell culture, leading to enhanced anti-BCMA and daratumumab-mediated myeloma cell killing. Additionally, Dr. Tai and her colleagues demonstrated that regulatory T cells in the blood and bone marrow expressed TACI, and that APRIL blockade inhibited their function. Also, John Dulos, Ph.D., director and project team leader at Aduro Biotech, and his team conducted preclinical pharmacokinetic and pharmacodynamic studies indicating BION-1301 was well tolerated and binding of APRIL in preclinical models resulted in decreased IgA, IgG and IgM production in a dose-dependent fashion.
Disease: relapsed or refractory multiple myeloma
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- This open-label, multi-center, dose-selection Phase 1/2 study is evaluating BION-1301, a humanized monoclonal antibody directed against APRIL for the treatment of relapsed or refractory multiple myeloma whose disease has progressed after at least 3 prior systemic therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors, chemotherapies, or monoclonal antibodies. This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and initial clinical activity of BION-1301 administered as a single agent.
- The study will be conducted in 2 parts. Phase 1 is dose escalation and seeks to determine the recommended phase 2 dose (RP2D). Once an RP2D is identified, Phase 2 of the study will open and continue to evaluate the safety and preliminary efficacy of BION-1301 administered at selected dose level(s).
- The population for this study will consist of adults with relapsed or refractory multiple myeloma whose disease has progressed after at least 3 prior systemic therapies. BION-1301 will be administered in 28-day cycles; the dosing interval will be once every two weeks. (NCT03340883)
Latest
news:
- • On December 18, 2017, Aduro Biotech announced that the first patient in its Phase 1/2 dose escalation and dose expansion clinical trial has been dosed at Virginia Cancer Specialists in Fairfax, Virginia, the first site in this multi-center trial. The study is designed to evaluate the safety and activity of BION-1301, a humanized anti-APRIL (A PRoliferation-Inducing Ligand) antibody, for adults with relapsed or refractory multiple myeloma.
- The Phase 1 part of the study will evaluate the safety, pharmacokinetics and pharmacodynamics of escalating doses of BION-1301 administered once every two weeks in a 28-day cycle. Once the recommended Phase 2 dose is determined, the Phase 2 part of the study will begin. It will assess safety and preliminary activity of BION-1301 at the selected dose, with a primary activity endpoint of objective response rate.
Is
general: Yes
