Pfizer Inc. has discontinued a phase III randomized, open-label, two-arm study (B1931008) evaluating the safety and efficacy of the investigational compound inotuzumab ozogamicin in patients with relapsed or refractory CD22+ aggressive non-Hodgkin lymphoma (NHL) who are not candidates for intensive high-dose chemotherapy. In this study, inotuzumab ozogamicin was administered on a once-a-month schedule in combination with rituximab and compared with an active comparator arm (investigator's choice of bendamustine plus rituximab or gemcitabine plus rituximab).
During a scheduled interim analysis, an independent Data Monitoring Committee (DMC) concluded that in this study treatment with inotuzumab ozogamicin plus rituximab would not meet the primary objective of improving overall survival (OS) when compared to the comparator arm. No new or unexpected safety issues were identified.
“We are working to better understand the findings from this review to determine if there are any patterns of outcome that may help us gain greater understanding of the potential effect of inotuzumab ozogamicin in specific patient subsets within the heterogeneous patient population enrolled in this trial,” said Dr Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs for Pfizer’s Oncology Business Unit. “Haematologic cancers are a complex group of diseases, with more than 70 different types of lymphomas, leukaemias or myelomas that require unique treatment options. We remain committed to evaluating inotuzumab ozogamicin in patients with haematologic malignancies.”
Pfizer has notified the study investigators and appropriate regulatory authorities of the decision to discontinue the study. Investigators will work with patients in the study on an individual basis to determine an appropriate course of action.
Inotuzumab ozogamicin, administered on a weekly basis, three weeks out of four, continues to be evaluated in adult acute lymphoblastic leukaemia (ALL). The INO-VATE ALL Study (B1931022) is an open-label, randomized, phase III study of inotuzumab ozogamicin compared to a defined investigator’s choice of chemotherapy in adult patients with relapsed or refractory CD22+ ALL.
ALL is one of the four main types of leukaemia. ALL is an aggressive type of leukaemia; without treatment, most patients with acute leukaemia would live only a few months.
Inotuzumab ozogamicin is an investigational antibody-drug conjugate (ADC) comprised of a monoclonal antibody (mAb) targeting CD22, a cell surface antigen expressed on approximately 90 per cent of B-cell malignancies, linked to a cytotoxic agent. When inotuzumab ozogamicin binds to the CD22 antigen on malignant B-cells, it is internalized into the cell, where the cytotoxic agent calicheamicin is released to destroy the cell.
Inotuzumab ozogamicin originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has responsibility for all manufacturing and development activities for this molecule.