Positive results have been reported from a phase 3, open-label, randomized study evaluating the safety and efficacy of inotuzumab ozogamicin (Pfizer/UCB) compared with investigator-choice chemotherapy in 326 adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL). The findings showed improvement over chemotherapy on a number of measures, including complete hematologic remission and progression-free survival (PFS). The data were published in the New England Journal of Medicine.
Inotuzumab ozogamicin is an investigational antibody–drug conjugate consisting of a monoclonal antibody targeting CD22, a cell-surface antigen found on cancer cells, linked to a cytotoxic agent, calicheamicin. When inotuzumab ozogamicin binds to the CD22 antigen on malignant B-cells, it is thought to be internalized into the cell, where the calicheamicin is released to destroy the cell.
The INO-VATE ALL trial had two independent primary endpoints: a complete response with or without hematologic remission and OS. The study met its first primary endpoint of a complete response, which was significantly better with inotuzumab ozogamicin compared with chemotherapy (80.7% vs. 29.4%, respectively; P < 0.001). Inotuzumab ozogamicin also significantly extended PFS compared with chemotherapy (hazard ratio [HR], 0.45; median PFS, 5.0 vs. 1.8 months, respectively; P < 0.001).
The second primary endpoint of OS showed a strong trend toward longer OS for patients treated with inotuzumab ozogamicin compared with chemotherapy but did not reach statistical significance (HR, 0.77; median OS, 7.7 months vs. 6.7 months, respectively; P = 0.0203). The two-year OS rate for inotuzumab ozogamicin was 23% compared with 10% for chemotherapy.
The results from the INO-VATE ALL trial also showed that 78.4% of patients treated with inotuzumab ozogamicin achieved minimal residual disease (MRD) negativity (78.4%) and experienced a duration of response (DOR) of 4.6 months (HR, 0.55). In comparison, 28.1% (P < 0.001) of patients treated with chemotherapy achieved MRD negativity, and the median DOR was 3.1 months (P < 0.034). Moreover, more patients proceeded to stem-cell transplant with inotuzumab ozogamicin compared with standard chemotherapy (41% vs. 11%; P < 0.001).
The most common adverse events (AEs) associated with both inotuzumab ozogamicin and chemotherapy were cytopenias, including febrile neutropenia (16% vs. 22%). Common nonhematologic treatment-emergent adverse events with inotuzumab ozogamicin included nausea (32%), headache (28%), and pyrexia (27%). Patients in the chemotherapy arm experienced nausea (47%), pyrexia (43%), and diarrhea (40%).
Veno-occlusive liver disease (VOD) of any grade occurred more often in patients treated with inotuzumab ozogamicin compared with those given chemotherapy (11% vs. 1%). Five patients taking inotuzumab ozogamicin developed VOD during treatment, and 10 patients developed VOD after subsequent stem-cell transplant. Among those taking chemotherapy, one patient developed VOD after transplant; no cases of VOD occurred during treatment with chemotherapy.
Inotuzumab ozogamicin received a breakthrough therapy designation from the FDA for the treatment of ALL in October 2015. ALL is an aggressive type of leukemia with a poor prognosis in adults. The current foundational treatment is intensive, long-term chemotherapy. It has been estimated that 6,590 cases of ALL will be diagnosed in the United States in 2016, with approximately two in five cases in adults. Approximately 20% to 40% of newly diagnosed adults with ALL are cured with current treatment regimens. For adult patients with relapsed or refractory ALL, the five-year overall survival rate is less than 10%.
Source: Pfizer; June 12, 2016.