The company said it has reported its decision to global health authorities, and is working closely with them, the safety monitoring committees, and the studies’ clinical investigators to assess all the data and determine the next steps for the AFM11 program.
AFM11 is a kind of antibody that binds to two targets at the same time: the CD19 protein found at the surface of B-cells and many leukemia and lymphoma cells, and the CD3 protein found on T-cells. This means that the antibody activates T-cells in the vicinity of tumor cells.
Interestingly, AFM11 has two binding sites for CD19 and two others for CD3, making it highly specific and eliminating some of the concerns of bispecific antibodies.
In preclinical studies, AFM11 showed twice as much response as other products used in the same setting. The medicine effectively prevented Burkitt’s lymphoma from progressing in mice by activating T-cells and causing the death of CD19-positive cancer cells.
Now on hold, the two Phase 1 trials assessing the investigational medicine include one for patients with B-cell non-Hodgkin’s lymphoma (NCT02106091) and another for patients with acute lymphoblastic leukemia (NCT02848911). Both trials were expected to include 50 participants with CD19-positive cancers and who had received at least one prior line of treatment.
To date, in both trials, a total of 33 patients have received AFM11, with preliminary signs of clinical activity reported in several patients. The patient who died and the two who experienced life-threatening events were all receiving the highest dose tested in each study.
According to the company, the temporary hold placed on the AFM11 trials will not affect the development of immunotherapies designed to trigger natural killer (NK) cells instead of T-cells, such as AFM13.
AFM13 targets the CD30 protein in lymphoma cells and the CD16A receptor at the surface of NK cells. It is currently in a Phase 2 trial for the treatment of Hodgkin’s lymphoma (NCT02321592) and CD30-positive lymphomas with skin manifestations (NCT03192202).