Study of Inotuzumab Ozogamicin Halted After Interim Analysis

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Mace Rothenberg, MD

Mace Rothenberg, MD

A phase III study of the investigational compound inotuzumab ozogamicin for patients with relapsed or refractory CD22+ aggressive non-Hodgkin lymphoma (NHL) who are not candidates for high-dose chemotherapy was halted after a scheduled interim analysis. The analysis found that the drug was unlikely to show an improvement in overall survival when compared with the control arm.

Inotuzumab ozogamicin is in a relatively new class of drugs known as antibody-drug conjugates. In this case, the monoclonal antibody inotuzumab targets the CD22 cell surface antigen, which is expressed on approximately 90% of B-cell malignancies.

Pfizer, the drug's manufacturer, launched a phase III randomized, open-label, two-arm study (B1931008) designed to compare inotuzumab ozogamicin on a once-a-month schedule in combination with rituximab with an active comparator arm that included an investigator’s choice of either bendamustine plus rituximab or gemcitabine plus rituximab. Pfizer reported that no new or unexpected safety issues had been identified in the study.

“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 Mace Rothenberg, MD, senior vice president of Clinical Development and Medical Affairs for Pfizer’s Oncology Business Unit, in a statement.

The efficacy of the combination of inotuzumab and rituximab was reported in the results of a phase I/II clinical trial, which were published earlier this year in theJournal of Clinical Oncology. In that study, 118 patients with either relapsed follicular lymphoma, relapsed diffuse large b-cell lymphoma (DLBCL), or refractory aggressive NHL received at least one and a median of four cycles of the inotuzumab-rituximab combination. At the maximum tolerated dose, the response rate was 87% in follicular lymphoma, 74% in DLBCL, and 20% in aggressive NHL. The study showed that the combination had a manageable safety profile, suggesting that it could be a promising treatment option for these patients.

Despite the continuation, Rothenberg said that it would continue to investigate the efficacy of inotuzumab ozogamicin in hematologic malignancies.

“Hematologic cancers are a complex group of diseases, with more than 70 different types of lymphomas, leukemias or myelomas that require unique treatment options,” Rothenberg said. “We remain committed to evaluating inotuzumab ozogamicin in patients with hematologic malignancies.”