Actinium Pharmaceuticals has announced the enrollment of the first patient in a groundbreaking clinical trial evaluating Iomab-ACT, a targeted radiotherapy conditioning agent, in combination with a commercial CAR-T therapy. The trial is being conducted at the University of Texas Southwestern Medical Center (UTSW), with initial clinical data expected in the second half of 2025.
Iomab-ACT represents a potential paradigm shift in CAR-T therapy conditioning, aiming to replace conventional chemotherapeutic conditioning agents such as Fludarabine and Cyclophosphamide (Flu/Cy). The novel approach targets CD45, a cell surface marker expressed on immune cells relevant to CAR-T therapy, including lymphocytes.
"We are thrilled to initiate patient enrollment to study Iomab-ACT targeted radiotherapy conditioning with a commercial CAR-T therapy," said Dr. Farrukh Awan, Professor of Medicine, Division of Hematology Oncology at UTSW. "Iomab-ACT is supported by compelling preclinical and clinical data, and we believe it has immense potential to eliminate the need for chemotherapy-based conditioning, which is a major barrier for many patients seeking CAR-T treatment."
Addressing Critical CAR-T Therapy Limitations
CAR-T therapies have revolutionized treatment for certain blood cancers, but significant challenges remain, particularly regarding toxicities and patient eligibility. Iomab-ACT aims to address serious CAR-T related toxicities, including immune effector cell-associated neurotoxicity (ICANS) and cytokine release syndrome (CRS), potentially improving both patient access and outcomes.
Preclinical data has demonstrated that Iomab-ACT can selectively target immune cells implicated in CAR-T toxicities while sparing bone marrow stem cells, red blood cells, and platelets. The agent produces transient lymphodepletion that aligns with the CAR-T treatment process.
These findings were supported by an NIH-funded trial conducted in collaboration with Memorial Sloan Kettering Cancer Center (MSK). In this study, Iomab-ACT was combined with a novel CD19 CAR-T therapy in heavily pretreated patients with relapsed and refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) or Diffuse Large B-cell Lymphoma (DLBCL). Notably, no patients (0/4) developed ICANS of any grade, and minimal CRS was observed. Additionally, Iomab-ACT demonstrated:
- Transient depletion of peripheral blood lymphocytes and monocytes
- Persistence of CAR T-cells up to 8 weeks
- Minimal non-hematologic toxicities
Market Potential and Strategic Importance
The CAR-T therapy landscape has expanded significantly in recent years, with seven approved therapies targeting CD19 for lymphoma and leukemia, and BCMA for multiple myeloma. These therapies generated over $4 billion in sales in 2024 and are forecasted to reach $12 billion in annual sales by 2030.
Currently, approximately 150,000 patients are diagnosed annually with conditions eligible for CAR-T therapies. The addressable patient population is expected to nearly double, reaching approximately 93,000 patients in the U.S. by 2030, based on the current pipeline of cellular therapies.
"This is a pivotal moment for our Iomab-ACT CD45 targeted radiotherapy conditioning program," stated Sandesh Seth, Actinium's Chairman and CEO. "Iomab-ACT is a highly differentiated conditioning agent that has produced promising initial clinical results where multiple targeted conditioning approaches including monoclonal antibodies and antibody drug conjugates directed against a variety of targets have not achieved clinical success to date."
Technical Mechanism and Differentiation
Iomab-ACT is the only clinical-stage conditioning agent targeting CD45. Its mechanism of action offers several potential advantages over conventional chemotherapy conditioning:
- Selective targeting of immune cells implicated in CAR-T toxicities
- Preservation of bone marrow stem cells and other critical blood components
- Transient lymphodepletion that aligns with the CAR-T treatment timeline
The company believes Iomab-ACT could become a universal targeted conditioning regimen for CAR-T and other cellular therapies, potentially creating a "blockbuster revenue opportunity" if it can provide clinical benefits related to adverse events, longer duration of response, or improved survival outcomes.
Broader Pipeline Context
Iomab-ACT is part of Actinium's broader portfolio of targeted radiotherapies. The company is also advancing:
- Actimab-A: A CD33 targeting therapeutic for acute myeloid leukemia (AML) and other myeloid malignancies
- ATNM-400: A novel non-PSMA targeting Ac-225 radiotherapy for prostate cancer
- Iomab-B: An induction and conditioning agent prior to bone marrow transplant in patients with relapsed/refractory AML
The company holds 230 patents and patent applications, including several related to the manufacture of the isotope Ac-225 in a cyclotron.
Looking Forward
With initial clinical data from the Iomab-ACT commercial CAR-T trial expected in the second half of 2025, Actinium is positioning itself at the forefront of innovation in targeted radiotherapy conditioning. If successful, this approach could significantly expand access to potentially curative CAR-T therapies while reducing treatment-related toxicities, addressing a critical unmet need in cancer care.
