Research findings of a clinical trial with IMGN529, a CD37-targeting antibody-drug conjugate or ADC being developed ImmunoGen, in combination with the CD20-targeting antibody rituximab (Rituxan®; Genentech/Roche ) as well as other CD20-targeting antibodies including obinutuzumab and ofatumumab, in preclinical assessments, shows that the investigational drug exhibits strong synergy with rituximab and other CD20-targeting antibodies in cell lines representative of an array of non-Hodgkin lymphoma (NHL) subtypes, including both GCB and ABC diffuse large B-cell lymphoma (DLBCL). The data was presented in a poster at the 13th International Conference on Malignant Lymphoma (ICML) taking place in Lugano, Switzerland (abstract #P-274) [1]
IMGN529 is being created for the treatment of B-cell malignancies. It consists of a CD37-binding antibody, K7153A conjugated to one of ImmunoGen’s potent cancer cell-killing agents, the maytansinoid anti-mitotic DM1. The antibody serves to deliver the DM1 specifically to B cells to kill them and, based on preclinical research, also contributes anticancer activity.
More than 70,000 people were diagnosed with non-Hodgkin lymphoma (NHL) in the United States in 2014 alone. [2] DLBCL is an aggressive lymphoma that represents approximately one third of the new NHL cases diagnosed annually. [3] GCB, or Germinal Center B-cell like, and ABC, or Activated B-cell like, are prevalent sub-types of diffuse large B-cell lymphoma or DLBCL which can differ markedly in their responses to treatment.
Combination with standard of care
The results of the preclinical assessment are consistent with the in vitro findings and research data in which the combination of IMGN529 and rituximab was highly active against DLBCL models in vivo. The synergy was also seen in vitro in a model representative of “double hit” lymphoma, a particularly difficult-to-treat type of DLBCL characterized by deregulation of two different genes, BCL2 (or BCL6) and MYC. Researchers noted that both IMGN529’s antibody component and its DM1 payload contributed to its synergistic activity with rituximab.
“Rituximab is a standard of care in the treatment of B-cell malignancies, and thus it is highly exciting that IMGN529 and rituximab demonstrate synergistic activity in combination in these models,” commented Charles Morris, M.B., Ch.B., M.R.C.P, Executive Vice President and Chief Development Officer of ImmunoGen. “We plan to initiate clinical testing of IMGN529 in combination with rituximab later this year to assess the potential benefit of such a regimen for patients with DLBCL.”
IMGN529 is currently in Phase I clinical testing for the treatment of NHL, used as a single agent in patients with heavily pre-treated disease. It has demonstrated encouraging evidence of activity, particularly for patients with relapsed/refractory DLBCL.[3]
Later this year, ImmunoGen plans to begin assessing IMGN529 used in combination with rituximab for the treatment of relapsed/refractory DLBCL in addition to assessing it as a single agent in DLBCL and chronic lymphocytic leukemia disease-specific patient populations.
