Swedish company BioInvent International has received verbal notice from the FDA that a full clinical hold (i.e., no further dosing of patients) has been placed on the company’s current phase 2 study of an immunotherapeutic antibody (BI-505) in patients with multiple myeloma. BioInvent has not yet received written notice of the clinical hold from the FDA; however, the agency stated that the hold was due to an adverse cardiopulmonary event in the study.
The trial is being conducted by BioInvent in collaboration with investigators at the University of Pennsylvania. Its objective is to document the ability of BI-505 to deepen the therapeutic response and thereby prevent or delay relapse in multiple myeloma patients undergoing autologous stem cell transplantation (ASCT) with high-dose melphalan.
BioInvent says it will analyze the possibility of obtaining a release of the clinical hold.
BI-505 is a human antibody that specifically binds to the intracellular adhesion molecule-1 (ICAM-1), affecting tumors in two ways: 1) by inducing apoptosis of myeloma cells and 2) by inducing the patient’s immune cells (macrophages) to attack myeloma cells, according to BioInvent. Macrophages are abundant in the bone marrow of myeloma patients, where they are thought to contribute to disease progression and the development of resistance to currently available drugs.
In a phase 1 study, published in 2015 in Clinical Cancer Research, BI-505 demonstrated a favorable safety profile in patients with advanced multiple myeloma. The disease was stable in approximately 25% of the subjects for at least two months.
In 2013, preclinical data published in Cancer Cell provided proof-of-concept for both BI-505 and BioInvent’s function-based F.I.R.S.T. platform. The article documented the activity of BI-505 in several preclinical multiple myeloma models.
BioInvent’s development strategy for BI-505 is focused on the treatment of patients with residual multiple myeloma in combination with current standard-of-care drugs. The randomized controlled phase 2 study that has been placed on clinical hold involves 90 patients undergoing ASCT and chemotherapy with high-dose melphalan. The study began with a safety evaluation of five patients. The study was designed to evaluate the clinical effect of BI-505 at 100 days after transplantation and after one year. All of the subjects will be monitored for up to three years to evaluate progression-free survival.
The FDA has granted BI-505 an orphan drug designation for the multiple myeloma indication.
Sources: BioInvent International; November 8, 2016; and BI-505; 2016.