Actinium’s phase 3 trial dosimetry results support low dose iomab-B for targeted lymphodepletion prior to adoptive cell therapy

Actinium Pharmaceuticals is advancing the development of low dose Iodine-131 apamistamab, a CD45 targeting antibody radiation-conjugate (ARC), as an alternative to today’s standard practice of chemotherapy-based lymphodepletion regimens like fludarabine/cyclophosphamide (Flu/Cy), which have been implicated in CAR-T toxicities including cytokine release syndrome (CRS) and neurotoxicity.

Actinium presented new findings from its pivotal Phase 3 SIERRA trial for Iomab-B (Iodine-131 apamistamab) at the 2019 American Society of Hematology (ASH) annual meeting on Sunday, December 8, 2019 in a poster presentation.

The analysis of dosimetric results with Iomab-B in the pivotal Phase 3 SIERRA trial was conducted to model a non-myeloablative dose level to be used for lymphodepletion prior to CAR-T, as well as the time frame in which an adoptive cell therapy such as CAR-T could be administered. Based on the results from 56 evaluable patients that received a dosimetric dose of Iodine-131 apamistamab, including patients initially randomized to receive Iomab-B and those that received Iomab-B upon crossover from the control arm, it was determined that a single 75 mCi dosage of Iodine-131 apamistamab would deliver approximately 200 cGy to the bone marrow, the threshold that is considered non-myeloablative. At this dose level, it expected that an adoptive cell therapy could be administered approximately six days following Iomab-ACT lymphodepletion. Actinium intends to advance its Iomab-ACT program into human proof-of-concept clinical trials in conjunction with an adoptive cell therapy. 

Dale Ludwig, Actinium’s Chief Scientific Officer, reminded that CAR-T, adoptive cell therapy, and gene therapy are revolutionary medical advances with great promise. However, he said, despite the innovation in these technologies, they continue to rely on generic chemotherapies for the necessary pre-conditioning prior to their administration, which are non-targeted and toxic. “We believe this restricts the true potential of these therapies by hindering their efficacy and durability while increasing toxicities such as cytokine release syndrome and neurotoxicity. With a starting clinical dose and time to clearance defined and supported by clinical results from the SIERRA trial, we look forward to our next step of advancing this program into human clinical testing with a cell therapy while continuing to introduce the Iomab-ACT program to cell and gene therapy developers,” he said.