FDA requests additional demonstration of OS benefit to support Iomab-B BLA in r/r acute myeloid leukemia
The FDA has determined that the findings from the phase III SIERRA trial (NCT02665065), despite meeting its primary end point of 6-month durable complete response (CR) rate, are not sufficient to support a biologics license application (BLA) filing for Iomab-B for patients with relapsed/refractory acute myeloid leukemia (AML), requesting an additional head-to-head randomized trial demonstrating an improvement in overall survival (OS)
Results from SIERRA, which had been previously presented at the 2023 Transplantation & Cellular Therapy Meetings, demonstrated a significant improvement in durable CR lasting 180 days or more with Iomab-B plus bone marrow transplant (BMT) vs physician’s choice of salvage chemotherapy and standard allogeneic BMT, at 22% (n = 13/76) vs 0% (n = 0/77), respectively (95% CI, 12.29%-34.73%; P < .0001).1,2 The 6-month event-free survival rate was also improved in the investigational arm, at 26% vs 0.2% with the control (HR, 0.22; 95% CI, 0.15-0.34; P < .0001). However, OS, which was a secondary end point, was not met in the intention-to-treat (ITT) analysis.
The FDA’s announcement was made after Actinium Pharmaceuticals concluded its clinical and chemistry, manufacturing, and controls discussions with the FDA regarding the BLA pathway for Iomab-B. The FDA is now recommending Actinium conduct a study comparing allogeneic BMT using Iomab-B plus a reduced-intensity conditioning (RIC) regimen of fludarabine and total-body irradiation with allogeneic BMT using RIC comprised of cyclophosphamide plus fludarabine and total-body irradiation. Additionally, the proposed study design will not allow crossover unlike the prior SIERRA trial, in which approximately 60% of patients crossed over to the investigational arm from the control arm, confounding OS results in the ITT population.
"While this is not the outcome we expected, we will work with the FDA to further discuss specifics of the proposed randomized head-to-head clinical study to determine its strategic feasibility. The 12 oral presentations of the SIERRA results at prestigious BMT, hematology, and nuclear medicine medical conferences in the United States and European Union are an attestation of the strong interest from the transplant community for better conditioning regimens due to the high unmet need,” stated Avinash Desai, MD, chief medical officer of Actinium.
Actinium intends to further consider additional details of the proposed clinical trial, which the regulatory agency suggested could be performed in all adult patients with AML
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