Phase III SIERRA study of Iomab-B shows efficacy in Acute Myeloid Leukemia.

Actinium Pharmaceuticals presented new data from the ongoing pivotal Phase III SIERRA study of Iomab-B (monoclonal antibody BC8 / I-131) single agent effect in patients with active, relapsed or refractory AML or Acute Myeloid Leukemia age 55 and above. The poster evaluated data from the first 25% of patients (38) from the SIERRA trial where a total of 29 patients received Iomab-B. This included 19 patients who received Iomab-B directly and 10 patients who received Iomab-B via crossover after conventional care salvage chemotherapy failed to produce a complete response. Previously presented preliminary feasibility data from the SIERRA trial demonstrated that all patients receiving Iomab-B had robust BMT or Bone Marrow Transplant donor engraftment and donor chimerism without delay.

The new data evaluated Iomab-B's effect as a single agent on white blood cells, lymphocytes and peripheral blasts. Of the 16 patients for whom data was available, there was a median reduction of peripheral blasts of 98% by day 3 and 100% reduction by day 8 following Iomab-B administration and prior to any other pre-BMT conditioning. Rapid reduction of peripheral blasts has been observed as an independent prognostic marker that is predictive of both CR or Complete Response and RFS or Relapse-Free Survival in patients with AML after receiving cytotoxic chemotherapy. Gianfaldoni et al1 performed an analysis of 30 newly diagnosed AML patients who were treated with cytotoxic induction chemotherapy and found that a rapid reduction of peripheral leukemia blasts correlated with responses and all patients that achieved CR had a rapid reduction of their peripheral blasts. Elliot et al2, performed a retrospective analysis of 86 adult patients with AML and identified time to clearance of circulating leukemia blasts as an independent prognostic marker of RFS that superseded all other known risk factors including karyotype and number of cycles of induction therapy needed to achieve CR.

The data was presented by SIERRA investigator Benjamin Tomlinson, M.D., Adult Hematologic and Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center (Cleveland, OH) in a poster presentation at the 2019 ASCO or American Society of Clinical Oncology Annual Meeting.

Comment: Iomab-B is an ARC or Antibody Radiation-Conjugate comprised of the anti-CD45 antibody apamistamab and the radioisotope iodine-131 that is intended to be a re-induction and conditioning agent prior to a BMT or bone marrow transplant. Iomab-B was developed at the Fred Hutchinson Cancer Research Center and has been studied in over 300 patients in multiple hematologic indications across 12 clinical trials in addition to the ongoing SIERRA study in older patients with active, relapsed or refractory AML or Acute Myeloid Leukemia prior to patients receiving an allogeneic BMT or bone marrow transplant.