Enrollment of the Phase 3 SIERRA trial of the Antibody-radiation Conjugate (ARC) 131I apamistamab (Iomab-B), being developed by Actinium Pharmaceuticals, has been completed.

Iomab-B includes the CD45 targeting antibody apamistamab, also known as BC8, conjugated to the radioisotope iodine-131.

The SIERRA trial is a 150-patient, randomized and controlled study conducted at 24 bone marrow transplant centers in the United States and Canada. SIERRA is the only randomized Phase 3 trial to offer bone marrow transplant (BMT) to patients with active, relapsed, or refractory acute myeloid leukemia (AML) age 55 and above, which is the only curative treatment option for patients diagnosed with this disease.

Data updates from the SIERRA trial in the fourth quarter of 2021 and to announce topline data for the primary endpoint of six-month durable Complete Remission (dCR) in mid-2022. These data are expected to support the registration of a Biologics License Application (BLA) for Iomab-B.

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Sergio A. Giralt, MD, Deputy Division Head, Division of Hematologic Malignancies; Melvin Berlin Family Chair in Multiple Myeloma at Memorial Sloan Kettering Cancer Center.

Significant advancement
“As an investigator in the SIERRA trial, I believe it is an important trial in the field of bone-marrow transplants, as Iomab-B represents a potentially significant advancement for BMT conditioning,”  noted Sergio A. Giralt, MD, Deputy Division Head, Division of Hematologic Malignancies; Melvin Berlin Family Chair in Multiple Myeloma at Memorial Sloan Kettering Cancer Center.

“Having spent my career working to expand the use of transplant and improve patient outcomes, I know firsthand the value of a targeted conditioning agent like Iomab-B can offer patients and transplant physicians. Given Iomab-B’s targeted nature, it has demonstrated the ability to produce effective myeloablation, even in patients with a high disease burden, while also being well-tolerated. This has shown to enable more patients, including those with significant comorbidities, to access bone marrow transplant and successfully engraft,” Giralt added.

Addressing unmet medical needs
“We are thrilled that the SIERRA trial is now fully enrolled. Since joining Actinium last November, I have ensured our clinical, CMC, and supply chain teams have been entirely focused on execution and on achieving this important milestone. Iomab-B was developed to address the significant unmet need of patients who could benefit and possibly be cured of their blood cancer with a bone marrow transplant but could not receive a transplant because non-targeted conditioning regimens could not produce a remission or are too toxic in this patient population,”  said Avinash Desai MD, Actinium’s Executive Vice President, Clinical Development, Operations.

“We are confident that Iomab-B will squarely address this unmet need given its targeted nature and ability to deliver high amounts of radiation directly to the bone marrow resulting in myeloablation while sparing healthy organs. The SIERRA trial was designed to evaluate the rate of dCR of at least six months in patients receiving Iomab-B and a BMT to those receiving salvage chemotherapy. With enrollment complete, we will turn our focus towards preparing a BLA submission to make Iomab-B available to the patients as soon as possible after receiving the topline results from the SIERRA trial. We sincerely thank the patients, their families, caregivers, staff, and investigators that participated in this important study,” Desai added.

“Completion of SIERRA enrollment is a major milestone for Actinium. It has been exciting seeing the trial conclude with strong momentum under Desai’s leadership. Through strong interactions with our sites, our revitalized clinical team has been able to successfully surmount obstacles that arose from the third wave of the COVID-19 pandemic and recruit the last 25% of patients faster than any previous cohort of patients. Their performance is a testament that our execution has never been stronger. We are eager to present additional data from SIERRA later this year and look forward to reporting topline data next year. As we look ahead, our team will be actively preparing a BLA to support regulatory approval of Iomab-B in patients with active r/r AML and executing market access and pre-commercial activities to support a potential U.S. launch,” noted Sandesh Seth, Actinium’s Chairman, and Chief Executive Officer.

“In addition, we will explore opportunities to expand the use of Iomab-B in other indications to support our targeted conditioning strategic business unit vision. Given that Iomab-B is the only CD45 targeting agent in clinical development, and that CD45 is expressed in all blood cancers, we believe there is a significant market opportunity. This multi-indication opportunity excites us as our commercial efforts would target a concentrated number of transplant centers and physicians that we believe will result in significant operating leverage. Beyond targeted conditioning, we will continue to leverage our targeted radiotherapy expertise, particularly in the field in the field of Actinium-225 based alpha therapies, to be at the forefront of innovation focused on bringing value to patients and investors,” Seth concluded.

Clinical trials
Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (SIERRA) – NCT02665065
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma – NCT04512716
Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome – NCT00589316

Featured Image: Human cells with acute myelocytic leukemia (AML) in the pericardial fluid, shown with an esterase stain at 400x.Courtesy: © This image was released by the National Cancer Institute, an agency part of the National Institutes of Health. Used with permission.

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