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The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for inotuzumab ozogamicin to treat adults with acute lymphoblastic leukemia (ALL).
Inotuzumab ozogamicin consists of a monoclonal antibody targeting CD22 and the cytotoxic agent calicheamicin.
When this antibody-drug conjugate binds to the CD22 antigen on malignant B cells, it is internalized, and calicheamicin is released to destroy the cell.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The FDA’s decision to grant inotuzumab ozogamicin breakthrough designation was based on results of the phase 3 INO-VATE ALL trial.
Results from this trial were presented at the 20th Congress of the European Hematology Association (EHA) last June (abstract LB2073*). The study is sponsored by Pfizer, the company developing inotuzumab ozogamicin.
This ongoing trial has enrolled 326 adult patients with relapsed or refractory, CD22-positive ALL. At EHA, Daniel DeAngelo, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, presented efficacy results in 205 patients and safety results in 259 patients.
Patients were assigned to receive inotuzumab ozogamicin (InO) or a defined set of chemotherapy choices (chemo). The InO schedule was once weekly for 3 weeks on a 3- to 4-week cycle for up to 6 cycles. Chemotherapy options included fludarabine, cytarabine, and G-CSF (FLAG); high-dose cytarabine (HIDAC); or cytarabine and mitoxantrone.
The primary endpoints of the study are hematologic remission, defined as a complete response with or without platelet and/or neutrophil recovery (CR/CRi), and overall survival. Survival data are not yet mature.
However, Dr DeAngelo reported that CR/CRi was significantly higher in the InO arm than the chemo arm—80.7% and 33.3%, respectively (P<0.0001). CR occurred in 35.8% and 19.8% of patients, respectively (P=0.0056), and CRi occurred in 45% and 13.5%, respectively (P<0.0001).
In both arms, most patients achieved CR/CRi during the first cycle of treatment—73% in the InO arm and 91% in the chemo arm.
The median duration of remission was 4.6 months in the InO arm and 3.1 months in the chemo arm (P=0.0169).
Overall, treatment-emergent adverse events (AEs) were similar between the arms. The incidence of any treatment-emergent AE was 98% in the InO arm and 99% in the chemo arm. The incidence of grade 3 or higher AEs was 91% and 95%, respectively. And the incidence of serious AEs was 48% and 46%, respectively.
Several AEs were more common in the chemo arm than the InO arm, including thrombocytopenia (61% vs 45%), anemia (53% vs 30%), febrile neutropenia (52% vs 27%), nausea (47% vs 32%), and pyrexia (42% vs 27%). The only AE that was more common in the InO arm than the chemo arm was AST increase (20% vs 10%).
There were 17 deaths in InO arm and 11 in the chemo arm. Four deaths in the InO arm and 2 in the chemo arm were considered treatment-related.
Causes of treatment-related deaths in the InO arm were acute respiratory distress syndrome as a terminal event of pneumonia (n=1), intestinal ischemia/septic shock (n=1), and veno-occlusive disease/ sinusoidal obstruction syndrome (n=2, both after post-study stem cell transplant). 
*Information in the abstract differs from the presentation.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for inotuzumab ozogamicin to treat adults with acute lymphoblastic leukemia (ALL).
Inotuzumab ozogamicin consists of a monoclonal antibody targeting CD22 and the cytotoxic agent calicheamicin.
When this antibody-drug conjugate binds to the CD22 antigen on malignant B cells, it is internalized, and calicheamicin is released to destroy the cell.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The FDA’s decision to grant inotuzumab ozogamicin breakthrough designation was based on results of the phase 3 INO-VATE ALL trial.
Results from this trial were presented at the 20th Congress of the European Hematology Association (EHA) last June (abstract LB2073*). The study is sponsored by Pfizer, the company developing inotuzumab ozogamicin.
This ongoing trial has enrolled 326 adult patients with relapsed or refractory, CD22-positive ALL. At EHA, Daniel DeAngelo, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, presented efficacy results in 205 patients and safety results in 259 patients.
Patients were assigned to receive inotuzumab ozogamicin (InO) or a defined set of chemotherapy choices (chemo). The InO schedule was once weekly for 3 weeks on a 3- to 4-week cycle for up to 6 cycles. Chemotherapy options included fludarabine, cytarabine, and G-CSF (FLAG); high-dose cytarabine (HIDAC); or cytarabine and mitoxantrone.
The primary endpoints of the study are hematologic remission, defined as a complete response with or without platelet and/or neutrophil recovery (CR/CRi), and overall survival. Survival data are not yet mature.
However, Dr DeAngelo reported that CR/CRi was significantly higher in the InO arm than the chemo arm—80.7% and 33.3%, respectively (P<0.0001). CR occurred in 35.8% and 19.8% of patients, respectively (P=0.0056), and CRi occurred in 45% and 13.5%, respectively (P<0.0001).
In both arms, most patients achieved CR/CRi during the first cycle of treatment—73% in the InO arm and 91% in the chemo arm.
The median duration of remission was 4.6 months in the InO arm and 3.1 months in the chemo arm (P=0.0169).
Overall, treatment-emergent adverse events (AEs) were similar between the arms. The incidence of any treatment-emergent AE was 98% in the InO arm and 99% in the chemo arm. The incidence of grade 3 or higher AEs was 91% and 95%, respectively. And the incidence of serious AEs was 48% and 46%, respectively.
Several AEs were more common in the chemo arm than the InO arm, including thrombocytopenia (61% vs 45%), anemia (53% vs 30%), febrile neutropenia (52% vs 27%), nausea (47% vs 32%), and pyrexia (42% vs 27%). The only AE that was more common in the InO arm than the chemo arm was AST increase (20% vs 10%).
There were 17 deaths in InO arm and 11 in the chemo arm. Four deaths in the InO arm and 2 in the chemo arm were considered treatment-related.
Causes of treatment-related deaths in the InO arm were acute respiratory distress syndrome as a terminal event of pneumonia (n=1), intestinal ischemia/septic shock (n=1), and veno-occlusive disease/ sinusoidal obstruction syndrome (n=2, both after post-study stem cell transplant).
*Information in the abstract differs from the presentation.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for inotuzumab ozogamicin to treat adults with acute lymphoblastic leukemia (ALL).
Inotuzumab ozogamicin consists of a monoclonal antibody targeting CD22 and the cytotoxic agent calicheamicin.
When this antibody-drug conjugate binds to the CD22 antigen on malignant B cells, it is internalized, and calicheamicin is released to destroy the cell.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The FDA’s decision to grant inotuzumab ozogamicin breakthrough designation was based on results of the phase 3 INO-VATE ALL trial.
Results from this trial were presented at the 20th Congress of the European Hematology Association (EHA) last June (abstract LB2073*). The study is sponsored by Pfizer, the company developing inotuzumab ozogamicin.
This ongoing trial has enrolled 326 adult patients with relapsed or refractory, CD22-positive ALL. At EHA, Daniel DeAngelo, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, presented efficacy results in 205 patients and safety results in 259 patients.
Patients were assigned to receive inotuzumab ozogamicin (InO) or a defined set of chemotherapy choices (chemo). The InO schedule was once weekly for 3 weeks on a 3- to 4-week cycle for up to 6 cycles. Chemotherapy options included fludarabine, cytarabine, and G-CSF (FLAG); high-dose cytarabine (HIDAC); or cytarabine and mitoxantrone.
The primary endpoints of the study are hematologic remission, defined as a complete response with or without platelet and/or neutrophil recovery (CR/CRi), and overall survival. Survival data are not yet mature.
However, Dr DeAngelo reported that CR/CRi was significantly higher in the InO arm than the chemo arm—80.7% and 33.3%, respectively (P<0.0001). CR occurred in 35.8% and 19.8% of patients, respectively (P=0.0056), and CRi occurred in 45% and 13.5%, respectively (P<0.0001).
In both arms, most patients achieved CR/CRi during the first cycle of treatment—73% in the InO arm and 91% in the chemo arm.
The median duration of remission was 4.6 months in the InO arm and 3.1 months in the chemo arm (P=0.0169).
Overall, treatment-emergent adverse events (AEs) were similar between the arms. The incidence of any treatment-emergent AE was 98% in the InO arm and 99% in the chemo arm. The incidence of grade 3 or higher AEs was 91% and 95%, respectively. And the incidence of serious AEs was 48% and 46%, respectively.
Several AEs were more common in the chemo arm than the InO arm, including thrombocytopenia (61% vs 45%), anemia (53% vs 30%), febrile neutropenia (52% vs 27%), nausea (47% vs 32%), and pyrexia (42% vs 27%). The only AE that was more common in the InO arm than the chemo arm was AST increase (20% vs 10%).
There were 17 deaths in InO arm and 11 in the chemo arm. Four deaths in the InO arm and 2 in the chemo arm were considered treatment-related.
Causes of treatment-related deaths in the InO arm were acute respiratory distress syndrome as a terminal event of pneumonia (n=1), intestinal ischemia/septic shock (n=1), and veno-occlusive disease/ sinusoidal obstruction syndrome (n=2, both after post-study stem cell transplant).
*Information in the abstract differs from the presentation.