Iomab-B (I-131-apamistamab) / Actinium, Immedica - LARVOL DELTA

Efficacy and safety of salvage therapies in relapsed/refractory Acute Myeloid Leukemia: A systematic review and network meta-analysis (ASH 2025) - "For safety, Cytarabine showed the lowest incidence of AEs (SUCRA = 0.71), while Enasidenib demonstrated the best profile in reducing mortality (SUCRA = 0.87). This NMA highlights Gilteritinib as the most effective and safest salvage therapy for R/R AML, particularly in patients with FLT3-mutated disease. Gemtuzumab Ozogamicin, Apamistamab, and Enasidenib also showed favorable outcomes, depending on molecular profiles and clinical priorities. These findings underscore the importance of individualized therapy selection based on efficacy, safety, and molecular characteristics."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3

131I-Apamistamab Effectively Achieved Durable Responses in Patients with R/R AML Irrespective of the Presence of Multiple High-Risk Factors (ASH 2023) - P3 | "Pts were randomized (1:1) to CC or 131I-apamistamab with fludarabine and total body irradiation (2 Gy) followed by alloHCT. Pts with R/R AML who have multiple risk factors such as adverse risk cytogenetics, age >65, venetoclax failure, high comorbidity index or poor KPS are typically not considered for alloHCT due to high transplant-related mortality and post-transplant relapse rates. 131I-apamistamab was effective in achieving durable responses in R/R AML pts irrespective of the presence of multiple risk factors and successfully enabled alloHCT in such pts due to its targeted mechanism of action."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

High-Dose Targeted Radiation with 131I-Apamistamab Prior to HCT Demonstrated a Dose-Response for Durable Complete Remission in Patients with R/R AML (ASH 2023) - P3 | "Pts were randomized (1:1, n=153) to CC or 131I-apamistamab with fludarabine and total body irradiation (2 Gy) followed by alloHCT. 131I-apamistamab led induction and conditioning followed by alloHCT resulted in statistically significant improvement in dCR at 6 mos vs conventional care. A dose-response was demonstrated for pts receiving 131I-apamistamab with those receiving a liver dose closer to the MTD of 24 Gy having about twice the dCR rate compared to pts 22 Gy (MTD-1) or less. We also found pts with higher marrow/liver ratio experienced considerably higher rates of dCR which highlights the importance of maximizing the dose to target tissues, within the limits of established risk organ dose tolerances."

Clinical • Acute Myelogenous Leukemia

131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant Significantly Improves Overall Survival in Patients with TP53 Mutated R/R AML (ASH 2023) - P3 | "Pts were randomized (1:1) to CC or 131I-apamistamab with fludarabine and total body irradiation (2 Gy) followed by alloHCT. Pts with TP53 mutated R/R AML have a dismal prognosis and are seldom offered alloHCT due to high post-transplant relapse rates. 131I-apamistamab led alloHCT significantly improves survival outcomes in pts with TP53 mutations, commensurate with rates observed in pts with wildtype TP53, thereby overcoming the negative impact of this mutation. These data clearly support the use of 131I-apamistamab led induction and conditioning and alloHCT in R/R AML, including in patients with a TP53 mutation."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • TP53

MED20-165: 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 (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD20

Humanization of Clinically Used Murine CD45 Antibody for Optimized CD45-Targeted Radioimmunotherapy (ASH 2024) - "Validating this approach, BC8 labeled with iodine-131 (131I-apamistamab [Iomab-B]) followed by allogeneic HCT was recently shown to improve outcomes of older adults with relapsed/refractory AML relative to conventional care...Our studies identify the antibody framework (with greatest efficacy so far observed with IgG1) and specific activity as critical factors for the efficacy of 211At-NCS-HuBC8. Together, these study support further development of HuBC8 as antibody for possible clinical RIT applications."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • PTPRC • UBE2H

Radioimmunotherapy Conditioning With 131I- Apamistamab for Allogeneic Transplant in Relapse/Refractory AML (RADAR) (clinicaltrials.gov) - P2/3 | N=306 | Not yet recruiting | Sponsor: Actinium Pharmaceuticals

New P2/3 trial • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

131I-apamistamab-based Conditioning for Hematopoietic Stem Cell Transplant (HSCT) in Advanced Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Columbia University

New P1 trial • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

NCI-2018-01788: 211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial primary completion date: May 2024 ➔ Jun 2027

Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • T Acute Lymphoblastic Leukemia • Transplantation • HLA-B • HLA-DRB1

Total Body Irradiation and Astatine-211-Labeled BC8-B10 Monoclonal Antibody for the Treatment of Nonmalignant Diseases (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Suspended ➔ Recruiting

Enrollment open • Oncology • HLA-A • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

Study of IOMAB-ACT Followed by CAR-T Cell Therapy for Patients Relapsed or Refractory (Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: University of Texas Southwestern Medical Center | Initiation date: Apr 2025 ➔ Jul 2025

Trial initiation date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

NCI-2018-01788: 211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial primary completion date: Jun 2027 ➔ May 2024

Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • T Acute Lymphoblastic Leukemia • Transplantation • HLA-B • HLA-DRB1

Study of IOMAB-ACT Followed by CAR-T Cell Therapy for Patients Relapsed or Refractory (Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Not yet recruiting ➔ Recruiting | Trial completion date: May 2029 ➔ May 2030 | Trial primary completion date: May 2028 ➔ May 2029

Enrollment open • Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Actinium receives orphan drug designation from FDA for Iomab-B in treating refractory and relapsed acute myeloid leukemia in elderly patients (Actinium Pharmaceuticals Press Release) - "Actinium Pharmaceuticals...announced...that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for Iomab-B, a radioimmunotherapeutic that conditions relapsed and refractory Acute Myeloid Leukemia (AML) patients for a Hematopoietic Stem Cell Transplant (HSCT), commonly referred to as a Bone Marrow Transplant (BMT). Iomab-B will soon begin a 150 patient, pivotal Phase 3 multicenter trial in relapsed and refractory AML patients over the age of 55."

Anticipated new P3 trial • Orphan drug • Oncology

Actinium Pharmaceuticals granted orphan designation from the European Medicines Agency for Iomab-B (GlobeNewswire) - "Actinium Pharmaceuticals...announced...that the Company’s lead asset, Iomab-B, has been granted orphan designation in the European Union (EU) by the European Medicines Agency (EMA). Iomab-B is intended to be used, upon approval, in preparing patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are over the age of 55 for a bone marrow transplant (BMT), often referred to as a hematopoietic stem cell transplant (HSCT)."

Orphan drug • Acute Myelogenous Leukemia • Oncology

NCI-2018-01788: 211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Mar 2027 ➔ Mar 2029 | Trial primary completion date: Jun 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • T Acute Lymphoblastic Leukemia • Transplantation • HLA-B • HLA-DRB1

Radioimmunotherapy of acute myeloid leukemia: a critical assessment of its prospects and limitations. (PubMed, Expert Rev Hematol) - "Its ability to target antigen negative LSC gives it an advantage compared with other forms of immunotherapy. In order to compete with other forms of targeted therapy the procedure has to be simplified."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Study of IOMAB-ACT Followed by Yescarta for Patients Relapsed or Refractory (Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: University of Texas Southwestern Medical Center

New P1/2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Iomab-B Regulatory Status and Program Update (PRNewswire) - "Actinium met with the FDA in the fourth quarter and aligned on the patient population for the head-to-head Phase 3 trial to evaluate allogeneic BMT using Iomab-B plus a reduced intensity conditioning regimen of fludarabine and total body irradiation (Flu/TBI) versus allogeneic BMT using reduced intensity conditioning comprised of cyclophosphamide plus Flu/TBI; Head-to-head Phase 3 trial to enroll adult patients aged 18 and above with active AML with blasts counts greater than 5% and less than 20%, representing a broader patient population than that in the SIERRA trial; Dose optimization trial to be completed prior to initiating the head-to-head Phase 3 trial to determine the dose for Iomab-B based on radiation to the bone marrow rather than the maximum tolerable dose of 24 Gy of radiation to the liver as was done in the SIERRA trial based on several interactions with the FDA before starting the SIERRA trial."

FDA event • New P3 trial • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Bone Marrow Dosimetry Exploratory Analysis from the Phase 3 SIERRA Trial of 131I-apamistamab Prior to HCT in Relapsed/Refractory Acute Myeloid Leukemia (EANM 2024) - "Materials and Patients 55 years or older with active relapsed/refractory AML were randomized (1:1) to receive 131I-apamistamab with fludarabine and total body irradiation (2 Gy) followed by HCT or conventional care (CC), with the potential to proceed to HCT if achieving CR. 131I-apamistamab based induction and conditioning followed by HCT resulted in statistically significant improvement in primary endpoint dCR at 6 months as a result of targeted radiation delivery with excellent safety. High doses of targeted radiation to the diseased marrow, greater than what would be achievable using total body irradiation, were safely delivered irrespective of age, performance status, sex and BMI."

P3 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Mucositis • Neutropenia • Oncology • Septic Shock

Modeling-based Assessment of Exposure Measurements After High-Dose Targeted 131I-apamistamab: Results and Analyses from the Phase III SIERRA Trial (EANM 2024) - "Exposure readings following radiation isolation showed considerable variability in clearance rate between patients, although no difference was seen in estimated time needed to reach release criteria by administered activity level, with a median of only 5 days even for patients receiving activities over 800 mCi. This ensured that patients were well below the 131I release criteria at the time of transplant, typically 12 days following the 131I-apamistamab infusion."

P3 data • Acute Myelogenous Leukemia

Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML. (PubMed, J Clin Oncol) - P3 | "The 131I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131I-apamistamab was well tolerated and could address an unmet need in this population."

Journal • P3 data • Acute Myelogenous Leukemia • Transplantation

Actinium Pharmaceuticals Announces Publication of Results from the Phase 3 SIERRA Trial of Iomab-B in the Journal of Clinical Oncology (PRNewswire) - P3 | N=153 | SIERRA (NCT02665065) | Sponsor: Actinium Pharmaceuticals | "Actinium Pharmaceuticals, Inc...announced the publication of the Phase 3 SIERRA results of Iomab-B in the peer-reviewed Journal of Clinical Oncology (JCO)....The SIERRA trial met the primary endpoint of durable Complete Remission (dCR) of 6-months following initial complete remission after BMT with high statistical significance (p-value of <0.0001) with 22% of patients (13/76) achieving dCR in the Iomab-B arm compared to 0% of patients (0/77) in the control arm. A significant improvement in Event Free Survival (EFS), a secondary endpoint of the SIERRA trial with a Hazard Ratio = 0.22 (p-value <0.0001) was also achieved. SIERRA did not meet the secondary endpoint of overall survival (OS) on an intent to treat basis analysis due to the high crossover rate with nearly 60% of control arm patients receiving Iomab-B followed by a BMT."

P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Long-Term Follow-up Demonstrates Ongoing Efficacy Benefit of (SOHO 2024) - P3 | "Patients were randomized (1:1, N=153) to CC or Iomab-B with fludarabine and total body irradiation (2 Gy) followed by alloHCT (CC, n=77; Iomab-B, n=76). The primary endpoint of dCR was improved in patients ≥55 y with active R/R AML receiving Iomab-B-led alloHCT versus CC. Most patients achieving dCR are long-term survivors. Improved outcomes in Iomab-B-treated patients persisted at longer follow-up."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • PTPRC

Actinium Provides Regulatory Update on Planned BLA Filing and Future Plans for Iomab-B in the U.S. (PRNewswire) - "Actinium will seek strategic partner for Iomab-B in the U.S. following completion of FDA interactions and focus development efforts on Actimab-A, Iomab-ACT and preclinical programs....Actinium Pharmaceuticals, Inc...announced a regulatory update on the Company's planned Biologics License Application ('BLA') filing for Iomab-B in patients with active relapsed or refractory acute myeloid leukemia ('r/r AML')....Despite the SIERRA trial meeting the primary endpoint of durable Complete Remission ('dCR') with statistical significance (p-value<0.0001) and other positive secondary endpoints including Event Free Survival ('EFS') and safety, the FDA has now determined that demonstrating an overall survival benefit in a randomized head-to-head trial is required for a BLA filing."

FDA event • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology