Pfizer announced that its phase 3 study investigating the treatment of inotuzumab ozogamicin achieved first primary endpoint of demonstrating a higher complete hematologic remission rate in adult patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL) compared to that achieved with standard of care chemotherapy.

The phase 3 study has two primary endpoints, complete hematologic remission rate and overall survival. Pfizer is continuing the study to allow for the data on overall survival to mature.

“We are excited about the results of the INO-VATE ALL study especially since relapsed and refractory acute lymphoblastic leukemia is a particularly difficult disease to treat in adults. The top-line results show that inotuzumab ozogamicin has the potential to be an important new treatment option for patients with relapsed or refractory disease,” said Dr Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology.

“We look forward to discussing these data with the FDA and other regulatory authorities.”

No new or unexpected safety issues were identified. Efficacy and safety data from this study will be submitted for presentation at an upcoming medical meeting.

The INO-VATE ALL study, also known as study 1022, is an open-label, randomized, phase 3 study evaluating the safety and efficacy of the investigational compound inotuzumab ozogamicin as compared with a defined set of chemotherapy choices in adult patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL).

The two primary endpoints are hematologic remission, defined as a complete response with or without platelet and/or neutrophil recovery (CR/CRi), and overall survival. Secondary endpoints include progression-free survival, volume of distribution and systemic clearance for inotuzumab ozogamicin in serum, duration of response, rate of stem-cell transplantation, minimal residual disease, cytogenetics, safety and quality of life (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Core-30 and EuroQual-5D Health Questionnaire).

Inotuzumab ozogamicin was administered intravenously once weekly for three weeks for a three to four week cycle up to six cycles. Chemotherapy options included fludarabine, cytarabine and G-CSF (FLAG); high dose cytarabine (HIDAC); or cytarabine and mitoxantrone.

There were 326 patients enrolled in the trial. Enrollment is now complete.

Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia with a poor prognosis in adults. The current foundational treatment is intensive, long-term chemotherapy. Approximately 20 to 40 percent of newly diagnosed adults with ALL are cured with current treatment regimens. For patients with relapsed or refractory adult ALL, the five-year overall survival rate is less than 10 percent.

Inotuzumab ozogamicin is an investigational antibody-drug conjugate (ADC) comprised of a monoclonal antibody (mAb) targeting CD22,7 a cell surface antigen expressed on approximately 90 percent 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 sole responsibility for all manufacturing and clinical development activities for this molecule.