The 150-subject, randomized, open-label, multi-center clinical trial will compare the combination regimen to RICE alone.
The primary endpoint is the comparison of complete remission rates between the two study arms.
Secondary endpoints include safety of the combination regimen, progression-free survival, overall survival and the number of patients who are ready for an autologous transplant.
Denintuzumab mafodotin is an antibody-drug conjugate (ADC) that targets CD19, a protein expressed uniformly on all B-cell malignancies.
The phase 2 trial is based on data from phase 1 study in B-cell non-hodgkin lymphoma.
Seattle Genetics chief medical officer and executive vice president for research and development Jonathan Drachman said: "In relapsed DLBCL patients in a phase 1 clinical trial, we have observed an objective response rate over 50 percent with denintuzumab mafodotin monotherapy and a tolerability profile that is well suited to combination regimens.
"Our preclinical data suggest that combining denintuzumab mafodotin with RICE may result in synergistic activity, potentially leading to improved treatment outcomes in relapsed or refractory DLBCL patients."
DLBCL is the most common type of non-Hodgkin lymphoma, which represents a group of cancers that develop in the lymphatic system.
They are characterized by uncontrolled growth and accumulation of abnormal lymphocytes, which will defend the body against infection.