Pfizer’s Phase III Results on Inotuzumab Ozogamicin Revealed!
Pfizer oncology, striving towards making the difference in the lives of cancer patients with their novel therapeutics presented their Phase III trial result of INO-VATE ALL study popularly known as study-1022 in the online issue of The New England Journal of Medicine.
This study was carried out on 326 adult patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL) to test the safety and efficacy of inotuzumab ozogamicin as compared with investigator’s-choice chemotherapy.
Figure 1. Diagram showing the cell that ALL starts in (Photo credit: Cancer Research UK / Wikimedia Commons).
Acute lymphoblastic leukemia (ALL) is uncontrolled proliferation of lymphocytes that crowds the bone marrow preventing it from making normal red blood cells, white blood cells, and platelets. About 6,000 people in the United States and mostly children under 15 years are diagnosed with this type of cancer.
Figure 2. Structure of inotuzumab ozogamicin (Photo credit: Thomas X, Dovepress, Volume 2014:4 Pages 1—8, ; //dx.doi.org/10.2147/BLCTT.S49048).
Inotuzumab ozogamicin is a monoclonal antibody (mAb) targeting CD22 which is a cell surface antigen found prominently in B cells of all ALL. This drug on binding to CD22 antigen on malignant B-cells gets internalized into the cell and cytotoxic agent calicheamicin is released to obliterate the tumor cell.
Figure 3. Mechanisms of action of inotuzumab ozogamicin (Photo credit: Thomas X, Dovepress, Volume 2014:4 Pages 1—8, ; //dx.doi.org/10.2147/BLCTT.S49048).
This study had two independent primary endpoints with overall survival and complete response with or without hematologic remission. The complete response end point was found to be highly significant with inotuzumab ozogamicin compared to chemotherapy. PFS was found to be significantly extended in inotuzumab ozogamicin compared to chemotherapy. The overall survival rate was found to be longer in patients administered with the drug. However, the level was not statistically significant.
Duration of response (DOR) of about 4.6 months was observed on the test patients while a DOR of 3.1 months was seen on patients at the chemotherapy wing. Minimal residual disease (MRD) negativity was found to be higher in patients taking the drug by 28.1% of the people undergoing chemotherapy.
However adverse effects such as cytopenias, including febrile neutropenia were observed in both the category. Other common adverse effects on consuming were nausea on 32%, headache 28% and pyrexia on 27% of the patients. In Patients receiving chemotherapy nausea on 47%, pyrexia on 43% and diarrhoea 40% were seen on the patients.
Any-grade veno-occlusive liver disease (VOD) was seen patients treated with inotuzumab ozogamicin. 5 of them developed during the treatment while 10 people developed during the subsequent treatment of stem cell transplant. No such case was reported in the chemotherapy treatment.
Hagop M. Kantarjian, M. D., lead study investigator and professor at The University of Texas MD Anderson Cancer Center announced, “Relapsed or refractory ALL is an aggressive leukemia in urgent need of new treatment options as about half of adult patients will not respond to chemotherapy or will see their disease return. The efficacy results seen in patients treated with inotuzumab ozogamicin in this study are impressive, particularly median progression-free survival, high rates of haematological remission and absence of minimal residual disease. These results suggest inotuzumab ozogamicin, if approved, could be a valuable new addition to currently available treatment options for ALL patients, including as a bridge to stem cell transplantation, which is the best chance for a cure at this stage of the disease.”
In October 2015, US FDA has designated inotuzumab ozogamicin as Breakthrough Therapy for ALL. Pfizer is actively working towards bringing the drug into market to treat people with relapsed or refractory CD22-positive ALL.