On November 6, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that new findings from its pivotal Phase 3 SIERRA trial for Iomab-B (Iodine-131 apamistamab) that support its Iomab-ACT program for lymphodepletion for CAR-T and adoptive cell therapies has been accepted for presentation at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting that is being held December 7-10, 2019 in Orlando, FL (Press release, Actinium Pharmaceuticals, NOV 6, 2019, View Source [SID1234550431]). Lymphodepletion is a necessary step that creates space for the CAR-T cells to be infused and promotes expansion of cells in vivo by creating a favorable homeostatic cytokine environment. Actinium is advancing the development of low dose Iomab-B (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.
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Title: Sierra Clinical Trial Dosimetry Results Support Low Dose Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] for Targeted Lymphodepletion Prior to Adoptive Cell Therapy
An analysis was performed on blood samples from 57 patients enrolled in the ongoing pivotal Phase 3 SIERRA trial for Iomab-B to demonstrate the effectiveness of low dose Iomab-B as a modality for targeted transient lymphodepletion. On the SIERRA trial, patients receive a low dosimetry dose of Iomab-B (median dose of 10 mCi with a range of 7-20 mCi) in an outpatient setting per study protocol. The analysis presented in the poster evaluated blood samples at various time points including pre-dosimetric infusion, post-dosimetric infusion, day 1 post-dosimetric infusion, and pre-therapeutic infusion (range 6-14 days post-dosimetry) to assess the impact of low dose Iomab-B on immune cell lymphodepletion and its anti-tumor effect on circulating blasts, as well as to determine its clearance profile from circulation.
Key Highlights:
– A significant but transient reduction in lymphocytes and white blood cells was observed compared to pre-dosimetry infusion levels
– 85% reduction in lymphocytes was observed at the post-dosimetry infusion time point, a 67% decrease at day 1 post-dosimetric infusion, and a 43% decrease one week later just prior to the Iomab-B therapeutic infusion
– 35% reduction in peripheral leukemic blasts was observed at the post-dosimetry infusion time point, suggesting a rapid anti-leukemic effect with single-agent Iomab-B consistent with findings from SIERRA presented at ASCO (Free ASCO Whitepaper) 2019
– The levels of platelets, red blood cells, and neutrophils were unchanged between pre-infusion and post-dosimetry infusion, potentially reflecting the comparatively lower surface antigen levels of CD45 on these cell types
– Based on an analysis of 25 treated patients, a non-myeloablative dose of 75 mCi has been proposed as a starting dose for human clinical testing
– Analysis of the proposed 75 mCi dose of Iomab-B would be sufficiently cleared in 136 hours (5.7 days) to allow for CAR-T administration
Poster Details:
Publication Number: 1958
Session Name: 704. Immunotherapies: Poster I
Date: Saturday, December 7, 2019
Presentation Time: 5:30 PM – 7:30 PM
Location: Orange County Convention Center, Hall B
Dale Ludwig, Ph.D., Actinium’s Chief Scientific Officer, said, "These promising findings from the analysis of clinical data from the SIERRA trial confirm our excitement and support the potential of our Iomab-ACT program as a chemotherapy-free alternative for lymphodepletion. While significant efforts have gone towards innovating CAR-T and cellular therapies, there has been little innovation in the lymphodepletion regimens that they rely on. These results show that the multi-modal mechanism of our CD45 targeting ARC can selectively deplete immune cells and exert an anti-leukemic effect while sparing red blood cells and platelets through a single-dose outpatient administration. It is exciting to see human clinical data produce these promising results and demonstrate that our Iomab-ACT program will fit well within the vein-to-vein time of CAR-T. We look forward to beginning a first-in-man clinical trial that will explore our Iomab-ACT program in conjunction with a CAR-T therapy and we have great confidence in continued positive results."
About the Iomab-ACT program
Iomab-ACT is a lower dose of Actinium’s lead program Iomab-B, which has been studied in over 300 patients and is currently being investigated in a pivotal Phase 3 trial for targeted conditioning prior to a Bone Marrow Transplant (BMT). Iomab-ACT targets CD45, an antigen expressed on many of the cells that are relevant to CAR-T including lymphocytes, macrophages and regulatory T-cells and that have been associated with CAR-T challenges such as durability of response, cytokine release syndrome (CRS) and neurotoxicity. Actinium has generated preclinical data that targeted lymphodepletion via Iomab-ACT has the potential to improve tumor control, selectively deplete necessary cells and be highly differentiated in terms of tolerability compared to chemotherapy-based lymphodepletion regimens, namely fludarabine/cyclophosphamide (Flu/Cy). The Iomab-ACT program may enable lymphodepletion through a single-dose outpatient administration versus Flu/Cy or other chemo-based lymphodepletion regimens that require multiple infusions in an inpatient setting over several days.