Actinium Publishes Phase 3 SIERRA Trial Results for Iomab-B in Clinical Oncology Journal

Actinium Pharmaceuticals, Inc., a leader in developing Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, has published the Phase 3 SIERRA trial results for Iomab-B in the Journal of Clinical Oncology. The SIERRA (Study of Iomab-B in Elderly Relapsed Refractory Acute Myeloid Leukemia) trial evaluated the effectiveness of Iomab-B in patients aged 55 and above with actively relapsed or refractory Acute Myeloid Leukemia (r/r AML). This trial was a significant step forward in finding alternatives to traditional chemotherapy for these patients.

The SIERRA trial was a randomized, multi-center, controlled study that enrolled 153 patients. It compared the outcomes of patients treated with Iomab-B followed by a bone marrow transplant (BMT) to those who received the physician’s choice of salvage chemotherapy and standard allogeneic BMT. Iomab-B is the first radiotherapy targeting CD45 for conditioning in development, aiming to facilitate potentially curative bone marrow transplants as an alternative to chemotherapy-dependent methods.

The trial successfully met its primary endpoint of achieving durable Complete Remission (dCR) six months post-initial remission following BMT. The statistical significance of this outcome was high, with 22% of patients in the Iomab-B arm achieving dCR compared to none in the control arm. Additionally, the trial showed a significant improvement in Event-Free Survival (EFS), another secondary endpoint.

However, the trial did not meet the secondary endpoint of overall survival (OS) on an intent-to-treat basis due to the high crossover rate, where nearly 60% of control arm patients received Iomab-B followed by a BMT. Despite this, the trial results have been presented at various leading medical meetings and congresses, revealing improved survival outcomes for patients with TP53 mutations and increased one- and two-year overall survival rates in patients aged 65 and above.

Dr. Sergio Giralt from Memorial Sloan Kettering Cancer Center, a leading investigator in the SIERRA trial, emphasized the significance of the trial in demonstrating that Iomab-B can improve access to potentially curative hematopoietic stem cell transplants compared to current chemotherapy-based regimens. He remarked on the importance of the trial's findings, noting the improved outcomes and significant unmet medical needs of elderly patients with relapsed or refractory AML. Despite the positive results, the SIERRA trial will not support the approval of Iomab-B on its own, highlighting the need for further trials to demonstrate overall survival benefits.

On August 5, 2024, Actinium disclosed that the FDA requires a randomized head-to-head trial to demonstrate an overall survival benefit for Iomab-B before its Biologics License Application (BLA) can be filed. This requirement means that the SIERRA trial results alone are insufficient for BLA submission.

Sandesh Seth, Actinium's Chairman and CEO, expressed excitement over the SIERRA results being published in a peer-reviewed journal, marking a significant advancement not just for the field of bone marrow transplant but more importantly for patients with relapsed and refractory AML. He looks forward to finalizing the details of an additional Phase 3 trial with the FDA and securing a U.S. partner to accelerate the availability of Iomab-B to patients in need.

Actinium Pharmaceuticals focuses on developing targeted radiotherapies aimed at improving survival for patients who have exhausted existing oncology treatments. Its pipeline includes Iomab-B, which serves as an induction and conditioning agent prior to bone marrow transplant, and Actimab-A, a therapeutic agent showing potential to extend survival for people with relapsed and refractory acute myeloid leukemia. Actinium holds numerous patents related to its innovative treatments and manufacturing processes.