Iomab-B Demonstrates Durable Remission in Relapsed/Refractory AML, Faces Regulatory Hurdles
核心洞察
The SIERRA trial showed that Iomab-B led to a significantly higher durable complete remission rate (17.1%) compared to conventional care (0%) in older patients with relapsed/refractory AML (搜索).
Despite positive results, the FDA has requested another randomized study before considering Iomab-B for approval, citing concerns about the initial trial design.
The new study should evaluate Iomab-B plus reduced-intensity conditioning versus a standard conditioning regimen, without crossover between treatment arms.
Treatment with Iomab-B (131I-apamistamab (搜索)), a CD45 (搜索)-targeted radiotherapy, resulted in higher durable complete remission (dCR) rates compared to conventional care in older patients with relapsed/refractory acute myeloid leukemia (搜索) (AML (搜索)). These findings come from the phase 3 SIERRA study (NCT02665065).
In the intent-to-treat population, the dCR rate was 17.1% (95% CI, 9.4%-27.5%) with Iomab-B compared to 0% (95% CI, 0%-4.7%) with conventional care, which consisted of salvage therapy followed by allogeneic hematopoietic cell transplant (alloHCT). This met the study’s primary endpoint. The hazard ratio for overall survival (OS) was 0.99 (95% CI, 0.70-1.41; P =.96), and the hazard ratio for event-free survival was 0.23 (95% CI, 0.15-0.34).
Grade 3 or higher treatment-related adverse effects were comparable between the two arms, with 59.7% and 59.2% of the Iomab-B and conventional care arms experiencing them, respectively.
Investigator Perspectives
"The SIERRA trial was important for the field of transplant and demonstrated for the first time in a randomized study that the CD45 (搜索) antibody-radioconjugate Iomab-B can provide patients with improved access to a potentially curative hematopoietic stem cell transplant, and improved outcomes compared [with] current chemotherapy-based regimens. Importantly, Iomab-B demonstrated a statistically significant improvement in key efficacy end points including durable complete remission and event-free survival," said Sergio Giralt, MD, deputy division head, Division of Hematological Malignancies, and attending physician, Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center, and SIERRA trial investigator.
Giralt added, “Despite multiple drug approvals for patients with AML (搜索), there remains no curative options for older patients with relapsed or refractory disease and outcomes for these patients also remain dismal. My fellow investigators and I are disappointed that the SIERRA trial will not support the approval of Iomab-B despite the positive results and significant unmet medical need of this patient population. However, there is continued significant interest from the transplant community to participate in the upcoming phase 3 study with Iomab-B to provide patients access to this important drug candidate.”
Regulatory Roadblock
In August 2024, the FDA communicated that the data from the SIERRA trial would not be sufficient to support a biologics license application and requested another randomized study for filing. The FDA recommended that Actinium Pharmaceuticals, the sponsor, conduct a study evaluating alloHCT using Iomab-B plus a reduced-intensity conditioning regimen of fludarabine and total-body irradiation versus alloHCT and reduced-intensity conditioning with cyclophosphamide, fludarabine, and total-body irradiation.
Additionally, the new study should not allow crossover. In the SIERRA trial, 44 of 77 patients crossed over from the conventional care arm to the Iomab-B arm, potentially confounding OS results.