IOMAB-ACT: a Phase Ib/II Multi-institutional Study of 131 I-Apamistamab Followed by CD19-targeted CAR-T Cell Therapy for Patients with Relapsed or Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL)

This study is being done to determine the safety, efficacy and tolerability of a single 50 mCi dose of 131I-Apamistamab given prior to CAR-T cell infusion in patients with Relapsed or refractory (R/R) Diffuse large B-cell lymphoma (DLBCL).

Start Date01 Apr 2025

Sponsor / Collaborator

The University of Texas Southwestern Medical Center

[+1]

NCT04512716

/ RecruitingEarly Phase 1IIT

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

This is a pilot study; patients will receive 131-I apamistamab prior to CAR T-cell infusion in order to determine the maximum tolerated dose of 131-I apamistamab is exceeded at 75 mCi, and if so, to assess the safety of a step-down dose of 50 mCi.

Start Date02 Feb 2021

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

NCT02665065

/ Active, not recruitingPhase 3

A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplant Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (AML)

The primary objective of this study is to demonstrate the efficacy of Iomab-B, in conjunction with a Reduced Intensity Conditioning (RIC) regimen and protocol-specified allogeneic hematopoietic stem cell transplant (HCT), versus Conventional Care in patients with Active, Relapsed or Refractory Acute Myeloid Leukemia (AML).

Start Date01 Jun 2016

Sponsor / Collaborator

Actinium Pharmaceuticals, Inc.

100 Clinical Results associated with I-131-Apamistamab

100 Translational Medicine associated with I-131-Apamistamab

100 Patents (Medical) associated with I-131-Apamistamab

Literatures (Medical) associated with I-131-Apamistamab

10 Jan 2025·JOURNAL OF CLINICAL ONCOLOGY

Randomized Phase III SIERRA Trial of ¹³¹ I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML

Article

Author: Schuster, Michael ; Pandit-Taskar, Neeta ; Abboud, Camille ; Foran, James ; Larkin, Karilyn ; Reddy, Vijay ; Lazarus, Hillard M. ; Koshy, Nebu ; Jamieson, Katarzyna ; Haeuber, Elaina ; Choe, Hannah ; Law, Arjun Datt ; Gyurkocza, Boglarka ; Rowley, Scott D. ; Litzow, Mark R. ; Tomlinson, Benjamin ; Silverman, Margarida ; Seropian, Stuart ; Orozco, Johnnie J. ; McNamara, Kathleen ; Sandmaier, Brenda M. ; MacDougall, James ; Desai, Avinash ; Pagel, John M. ; Spross, Jennifer ; Levy, Moshe Y. ; Sabloff, Mitchell ; Munshi, Pashna ; Hari, Parameswaran ; Cook, Rachel ; Van Besien, Koen ; Stiff, Patrick ; Kebriaei, Partow ; Giralt, Sergio ; Abhyankar, Sunil ; Vusirikala, Madhuri ; Nahar, Akash ; Chen, George ; Al-Kadhimi, Zaid ; Nath, Rajneesh

PURPOSE:

Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate 131 I-apamistamab with conventional care.

METHODS:

SIERRA (ClinicalTrials.gov identifier: NCT02665065 ) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an 131 I-apamistamab–led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the 131 I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131 I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population.

RESULTS:

The ITT population included 153 patients ( 131 I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131 I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131 I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring 131 I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131 I-apamistamab and conventional care groups, respectively.

CONCLUSION:

The 131 I-apamistamab–led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131 I-apamistamab was well tolerated and could address an unmet need in this population.

17 Jan 2024·Clinical cancer research : an official journal of the American Association for Cancer Research

Targeted Radiation Delivery before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-term Survivors

Article

Author: Wilbur, D. Scott ; Green, Damian J. ; Pagel, John M. ; Hamlin, Donald K. ; Haaf, Robyn L. ; Fisher, Darrell R. ; Vo, Phuong T. ; Orozco, Johnnie J. ; Sandmaier, Brenda M. ; Gopal, Ajay K. ; Gooley, Ted A. ; Matesan, Manuela C. ; Lundberg, Sally J.

Abstract:

Purpose::

Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase I/II study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML or ALL), or myelodysplastic syndrome (MDS; ClinicalTrials.gov, NCT00589316).

Patients and Methods::

Patients received a tracer diagnostic dose before a therapeutic infusion of 131Ianti-CD45 to deliver escalating doses (12–26 Gy) to the dose-limiting organ. Patients subsequently received fludarabine, cyclophosphamide (CY), and 2 Gy TBI conditioning before haploidentical marrow HCT. GVHD prophylaxis was posttransplant CY plus tacrolimus and mycophenolate mofetil.

Results::

Twenty-five patients (20 with AML, 4 ALL and 1 high-risk MDS) were treated; 8 had ≥ 5% blasts by morphology (range 9%–20%), and 7 had previously failed HCT. All 25 patients achieved a morphologic remission 28 days after HCT, with only 2 patients showing minimal residual disease (0.002–1.8%) by flow cytometry. Median time to engraftment was 15 days for neutrophils and 23 days for platelets. Point estimates for overall survival and progression-free survival were 40% and 32% at 1 year, and 24% at 2 years, respectively. Point estimates of relapse and nonrelapse mortality at 1 year were 56% and 12%, respectively.

Conclusions::

131I-anti-CD45 radioimmunotherapy prior to haploidentical HCT is feasible and can be curative in some patients, including those with disease, without additional toxicity.

04 May 2022·Expert opinion on biological therapyQ3 · MEDICINE

Where do we stand with radioimmunotherapy for acute myeloid leukemia?

Q3 · MEDICINE

Article

Author: Walter, Roland B

INTRODUCTION:

Despite the approval of several new drugs, deaths from acute myeloid leukemia (AML) remain common. Because of well-defined cell surface antigens, easy accessibility, and radiosensitivity of leukemia cells, there is long-standing interest in radiolabeled antibodies (radioimmunotherapy [RIT]) to complement or replace existing treatments and improve outcomes in AML.

AREAS COVERED:

Targeting primarily CD33, CD45, or CD66, early RIT efforts have focused on β-emitters, including iodine-131 (¹³¹I) and yttrium-90, mostly to intensify conditioning therapy before allogeneic hematopoietic cell transplantation (HCT). An ¹³¹I-labeled CD45 antibody (Iomab-B [apamistamab-I131]) is currently studied in the registration-type phase 3 SIERRA trial (NCT02665065) for this purpose. Of growing interest as therapeutic payloads are α-particle emitting radionuclides such as actinium-225 (²²⁵Ac) or astatine-211 (²¹¹At) since they deliver substantially higher decay energies over a much shorter distance than β-emitters, rendering them more suitable for precise, potent, and efficient target cell killing while minimizing toxicity to surrounding bystander cells, possibly allowing use outside of HCT. Clinical efforts with ²¹¹At-labeled CD45 antibodies and ²²⁵Ac-labeled CD33 antibodies (e.g. ²²⁵Ac-lintuzumab [Actimab-A]) are ongoing.

EXPERT OPINION:

A first anti-AML RIT may soon become available. This might propel further work to develop RIT-based treatments for AML, with many such efforts already ongoing.

News (Medical) associated with I-131-Apamistamab

18 Nov 2024

·www.prnewswire.com

Actinium Pharmaceuticals Highlights Antibody Radiation Conjugate Program Developments and Reports Financial Results for the Third Quarter 2024

- Aligned with FDA on operationally seamless Phase 2/3 trial for Actimab-A + CLAG-M in relapsed/refractory acute myeloid leukemia - Actimab-A selected for National Cancer Institute's recently opened myeloMATCH precision medicines program for patients with acute myeloid leukemia and myelodysplastic syndromes - Two Iomab-ACT INDs cleared by FDA: Commercial CAR-T trial at University of Texas Southwestern and sickle cell transplant trial at Columbia University; proof-of-concept safety and efficacy data expected in 2025 - Actinium seeking U.S. strategic partner for Iomab-B to conduct dose optimization and head-to-head Phase 3 trial based on FDA guidance in adult patients with active relapsed or refractory acute myeloid leukemia - Accomplished biopharma industry executive June Almenoff, M.D., Ph.D., appointed to Actinium's Board of Directors - Cash and cash equivalents of approximately $78.6 million as of September 30, 2024, is expected to fund operations into 2027 NEW YORK, Nov. 18, 2024 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, today highlighted recent regulatory and development updates for its Iomab-B, Actimab-A and Iomab-ACT ARC clinical programs as well as its financial results for the third quarter ended September 30, 2024. Iomab-B is a first in class CD45 targeted conditioning agent to enable bone marrow transplant (BMT) and has been studied in over four hundred patients including the completed Phase 3 SIERRA trial for patients with relapsed or refractory acute myeloid leukemia (r/r AML). Actimab-A is a targeted radiotherapeutic that uses the Actinium-225 (Ac-225) isotope payload directed against CD33 with broad potential for development in AML and other myeloid indications including in collaboration with the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA). Iomab-ACT is a next-generation CD45 targeted conditioning agent being developed for cell and gene therapies for both malignant and non-malignant hematologic indications. Actinium is executing cutting-edge R&D focused on ARCs and other targeted radiotherapies for blood cancer and solid tumor indications leveraging its strong intellectual property portfolio of 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. Sandesh Seth, Actinium's Chairman and CEO, stated, "During the third quarter and over the last several weeks, we have made significant progress with our three ARC clinical programs. Actinium is now positioned to advance exciting clinical trials for Actimab-A and Iomab-ACT in large indications with high unmet needs that can deliver impactful clinical data in 2025. Actimab-A's backbone therapy potential is poised to be realized with the operationally seamless Phase 2/3 trial following alignment with the FDA, additional clinical trials being planned under the NCI CRADA including the myeloMATCH program and via our R&D efforts to further elucidate Actimab-A's mutation agnostic mechanism of action. The clinical data anticipated from Iomab-ACT in 2025 from the commercial CAR-T and sickle cell transplant trials has the potential to establish Iomab-ACT as a best-in-class targeted conditioning agent for both malignant and non-malignant hematology indications. In addition, our recent meeting with the FDA regarding Iomab-B established a clear development pathway, which will be incredibly valuable in securing a U.S. strategic partner. Finally, I am delighted to welcome Dr. June Almenoff to our Board of Directors, who brings over 25 years of biopharma industry experience with a proven track record of leading drug development through approvals and executing value enhancing business development transactions." Actimab-A Regulatory and Development Update Actinium met with the FDA in the third quarter and aligned with the FDA on an operationally seamless randomized Phase 2/3 trial to study Actimab-A + CLAG-M In the Phase 2 portion of the study, the Actimab-A dose will be optimized in combination with CLAG-M The Phase 3 portion will study the optimized dose of Actimab-A + CLAG-M versus CLAG-M alone in patients with r/r AML Operationally seamless trial design is expected to reduce the required time and resources compared to separate Phase 2 and Phase 3 trials Actinium continues to evaluate and develop additional Actimab-A clinical trials under its CRADA with the NCI, investigator initiated, or Actinium sponsored studies Actimab-A selected by NCI for recently opened myeloMATCH precision medicine program for patients with AML and myelodysplastic syndrome (MDS) Iomab-ACT Program Update In the third quarter, the FDA cleared the investigational new drug (IND) applications for both the commercial CAR-T study led by the University of Texas Southwestern (UTSW) and the sickle cell trial being led by Columbia University The UTSW commercial CAR-T trial expected to initiate patient enrollment in 1Q 2025 with proof-of-concept clinical data expected by year end Commercial CAR-T sales exceeded $3.5 billion in 2023 with multiple CAR-T therapies approved for patients with lymphomas, leukemias and multiple myeloma Columbia University sickle cell transplant trial to study Iomab-ACT for targeted conditioning prior to BMT for the first time in a non-malignant hematology setting, which is a rapidly growing indication for BMT; patient enrollment expected to commence in the first half of 2025 Iomab-B Regulatory Status and Program Update Actinium is seeking a U.S. strategic partner to advance clinical development of Iomab-B including the Phase 3 trial 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 Mr. Seth added, "We are excited by our recent progress and committed to delivering on several milestones in the near-term and throughout 2025. Our current balance sheet provides strong runway into 2027, which enables us to deliver important clinical data and further realize our vision of being a leading fully integrated specialty radiopharmaceutical company." Third Quarter 2024 Financial Results Cash and cash equivalents of approximately $78.6 million as of September 30, 2024. Based on Actinium's current operating plan, cash and cash equivalents are expected to fund operations into 2027. Research and Development Expense, net of reimbursements Research and development expenses of $9.8 million for the three months ended September 30, 2024 decreased $1.8 million from $11.6 million for the three months ended September 30, 2023. The decrease is primarily a result of a decline in Chemistry, manufacturing and controls, or CMC, expenses of $5.5 million and lower consulting expenses of $0.5 million, both due to lower activity in 2024 related to Iomab-B. These declines were partially offset by increased preclinical expenses of $3.9 million. General and administrative expense General and administrative expenses of $2.8 million for the three months ended September 30, 2024 increased by $0.1 million from $2.7 million for the three months ended September 30, 2023, primarily due to higher non-cash stock compensation expense of $0.5 million, partially offset by lower compensation expense of $0.3 million due to lower headcount. In the third quarter of 2024, our overall headcount reduced by approximately twenty percent, with a majority of these former employees being from our clinical and CMC groups. As a result of these departures, we expect our personnel expenses to be reduced by approximately $3.7 million in 2025, which may be offset by additional hires or consultants. We do not expect these departures to have a material impact on our operations or ability to execute our operating plan and we are actively seeking a strategic partner for Iomab-B in the U.S. to advance the clinical development activity for Iomab-B including the planned Phase 3 trial. Other income Other income is comprised of net interest income in both reporting periods. The amount for the three months ended September 30, 2024 and 2023 of $1.0 million in each reporting period was virtually unchanged from the same time period in the prior year. Net loss Net loss of $11.6 million for the three months ended September 30, 2024 decreased by $1.7 million from $13.3 million for the three months ended September 30, 2023 due to lower research and development expenses partially offset by higher general and administrative expenses. About Actinium Pharmaceuticals, Inc. Actinium develops Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies intended to meaningfully improve outcomes for people who have failed existing oncology therapies. The company continues to advance its development for product candidate Actimab-A, a therapeutic agent that has demonstrated potential activity in r/r AML patients. In addition, Actinium is engaged with the National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) for development of Actimab-A in AML and other myeloid malignancies. Iomab-ACT, Actinium's next generation conditioning candidate, is being developed with the goal of improving patient access and outcomes for potentially curative cell and gene therapies. Iomab-B is an induction and conditioning agent prior to bone marrow transplant in patients with relapsed and refractory acute myeloid leukemia (r/r AML), which Actinium is seeking a potential strategic partner for in the U.S. In addition, the company's R&D efforts are primarily focused on advancing several preclinical programs for solid tumor indications. Actinium holds 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. For more information, please visit: Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: [email protected] SOURCE Actinium Pharmaceuticals, Inc. 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Phase 3Financial StatementPhase 2Radiation Therapy

25 Oct 2024

·www.immedica.com

Data from the phase 3 SIERRA trial of Iomab-B presented at the annual European Association of Nuclear Medicine (EANM) Congress 2024

Stockholm, October 25, 2024 – Immedica is pleased to announce that data from the Phase 3 SIERRA trial of Iomab-B was presented in both an oral and a poster presentation at the 2024 European Association of Nuclear Medicine (EANM) Congress, held in Hamburg from October 19-23. Immedica is collaborating with Actinium Pharmaceuticals on the development of Iomab-B. Dr. Neeta Pandit-Taskar, Molecular Imaging and Therapy, Memorial Sloan Kettering Cancer Center, New York, U.S. presented the results: Details of the EANM oral presentation: Title (OP-097): “Modeling-based Assessment of Exposure Measurements After High-Dose Targeted 131I-apamistamab: Results and Analyses from the Phase III SIERRA Trial” Session: Cutting Edge Science Track - Featured Session: Radiation Protection Committee / EARL: Radiation Protection for Radionuclide Therapy and Animal Protection Date and Time: October 20, 2024, 09:45 – 11:15 (CET), Hall Y4-Y9 Details of the EANM e-poster presentation: Title (EPS-134): Bone Marrow Dosimetry Exploratory Analysis from the Phase 3 SIERRA Trial of 131I-apamistamab Prior to HCT in Relapsed/Refractory Acute Myeloid Leukemia Session: e-Poster Presentations Session 7: Dosimetry Committee: Evolving Dosimetry Strategies Date and time: October 21, 2024, 15:00 – 16:30 (CET), Hall F. About EANM meeting The EANM Annual Meeting is the premier event for professionals in the field of nuclear medicine, bringing together experts from around the world to discuss the latest advancements, research, and innovations. The meeting provides a platform for sharing knowledge, fostering collaboration, and exploring new developments in diagnostic imaging, radionuclide therapies, and molecular medicine. About Actinium Pharmaceuticals, Inc. Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidate Iomab-B is an induction and conditioning agent prior to bone marrow transplant. Actinium holds more than 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. For more information, please visit: https://www.actiniumpharma.com/ About Immedica Immedica is a pharmaceutical company, headquartered in Stockholm, Sweden, focused on the commercialization of medicines for rare diseases and specialty care products. Immedica’s capabilities cover marketing and sales, compliance, pharmacovigilance, quality assurance, regulatory, medical affairs and market access, as well as a global distribution network serving patients in more than 50 countries. Immedica is fully dedicated to helping those living with diseases which have a large unmet medical need. Immedica’s therapeutic areas are within genetic & metabolic diseases, hematology & oncology and specialty care. Immedica was founded in 2018 and employs today more than 140 people across Europe, the Middle East and the U.S. The main owners are the investment firms KKR and Impilo. For more information visit www.immedica.com Immedica contact: Linda Holmström Head of Communication linda.holmstrom@immedica.com + 46 708 73 40 95 We believe we have an important role to fill in society – bringing new, innovative treatments to patients with rare diseases. Focus areas are within genetic & metabolic diseases, hematology & oncology and specialty care. We operate products from phase 2 and all the way to mature products. ESG is an integrated part of our business model. Stay up to date with our latest news. Telephone: +46 (0) 8 533 39 500 E-mail: info@immedica.com

Phase 3Clinical ResultRadiation Therapy

20 Sep 2024

·www.prnewswire.com

Actinium Pharmaceuticals Announces Publication of Results from the Phase 3 SIERRA Trial of Iomab-B in the Journal of Clinical Oncology

Iomab-B is the first CD45 targeted radiotherapy for conditioning in development to enable potentially curative bone marrow transplant and represents an alternative to chemotherapy-based approaches SIERRA achieved durable Complete Remission primary endpoint and Event-Free Survival secondary endpoint with high statistical significance Iomab-B was well tolerated in the older, heavily pretreated relapsed/refractory AML patients with active disease enrolled in the SIERRA trial Actinium to seek strategic partner for Iomab-B for further development in the U.S. following completion of interactions with FDA for additional head-to-head clinical trial to demonstrate overall survival benefit NEW YORK, Sept. 20, 2024 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, today announced the publication of the Phase 3 SIERRA results of Iomab-B in the peer-reviewed Journal of Clinical Oncology (JCO). The article, titled, "Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation vs Conventional Care for Relapsed/Refractory Acute Myeloid Leukemia" and is available online on the ASCO Journal of Clinical Oncology website HERE. The Phase 3 SIERRA ( Study of Iomab-B in Elderly Relapsed Refractory AML) trial was a randomized, multi-center, controlled trial that enrolled 153 patients aged 55 and above with active relapsed or refractory Acute Myeloid Leukemia (r/r AML), including heavily pre-treated patients and those with high-risk characteristics such as a TP53 mutation. The SIERRA trial compared outcomes of patients receiving Iomab-B (Iodine-131-apamistamab) and a bone marrow transplant (BMT) to physician's choice of salvage chemotherapy and standard allogeneic BMT in the control arm. 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. The Phase 3 SIERRA results were first presented in a late-breaker presentation at the Transplantation & Cellular Therapy (TCT) Tandem Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR) in February 2023. Since TCT, the results of the SIERRA trial have been presented in several oral presentations at leading BMT, hematology, nuclear medicine and nursing meetings and congresses in the U.S. and EU. Supplemental analyses of the SIERRA results have shown improved survival outcomes in patients with a TP53 mutation, which is associated with poor outcomes, as well as increased 1-and 2-year overall survival in patients aged 65 and above. Dr. Sergio Giralt, Deputy Division Head, Division of Hematological Malignancies and Attending Physician, Adult BMT Service at the Memorial Sloan Kettering Cancer Center, and leading SIERRA Trial investigator and corresponding author, said, "The SIERRA trial was important for the field of transplant and demonstrated for the first time in a randomized study that the CD45 antibody-radioconjugate Iomab-B can provide patients with improved access to a potentially curative hematopoietic stem cell transplant, and improved outcomes compared to current chemotherapy-based regimens. Importantly, Iomab-B demonstrated a statistically significant improvement in key efficacy endpoints including durable Complete Remission and event-free survival. The SIERRA trial was conducted as multiple new therapies gained approval and was designed to address the nuances and difficulty of treating this patient population including allowing physician's choice of care in the control arm given the heterogeneity of treatment across institutions and the crossover design to provide best patient care. Despite multiple drug approvals for patients with AML, there remains no curative options for older patients with relapsed or refractory disease and outcomes for these patients also remain dismal. My fellow investigators and I are disappointed that the SIERRA trial will not support the approval of Iomab-B despite the positive results and significant unmet medical need of this patient population. However, there is continued significant interest from the transplant community to participate in the upcoming phase 3 study with Iomab-B to provide patients access to this important drug candidate." On August 05, 2024, Actinium announced that after concluding both its clinical and Chemistry, Manufacturing and Controls ("CMC") interactions with the FDA regarding the BLA pathway for Iomab-B, the FDA determined that demonstrating an overall survival benefit in a randomized head-to-head trial is required for a BLA filing, and the SIERRA trial alone will not be adequate for BLA filing. Sandesh Seth, Actinium's Chairman and CEO, stated, "We are excited that the SIERRA results have been published in the peer-reviewed Journal of Clinical Oncology. We believe the SIERRA trial was a major advancement for the field of BMT and targeted radiotherapeutics but most importantly for patients with relapsed and refractory AML. We look forward to completing our interactions with the FDA to finalize the specifics of the additional Phase 3 randomized trial and working to secure a U.S. partner for Iomab-B. In doing so, we hope to accelerate Iomab-B reaching patients with high unmet need that can benefit from a bone marrow transplant." About Actinium Pharmaceuticals, Inc. Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B, an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic agent, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium holds more than 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. For more information, please visit: Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: [email protected] SOURCE Actinium Pharmaceuticals, Inc. 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Phase 3Clinical Result

100 Deals associated with I-131-Apamistamab

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Refractory acute myeloid leukemia	Phase 3	US	Actinium Pharmaceuticals, Inc.	01 Jun 2016
Refractory acute myeloid leukemia	Phase 3	CA	Actinium Pharmaceuticals, Inc.	01 Jun 2016
Relapsing acute myeloid leukemia	Phase 3	US	Actinium Pharmaceuticals, Inc.	01 Jun 2016
Relapsing acute myeloid leukemia	Phase 3	CA	Actinium Pharmaceuticals, Inc.	01 Jun 2016
Diffuse Large B-Cell Lymphoma	Phase 2	US	Actinium Pharmaceuticals, Inc.	01 Apr 2025
Diffuse Large B-Cell Lymphoma	Phase 2	US	The University of Texas Southwestern Medical Center	01 Apr 2025

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SNMMI2024	Not Applicable	-	-	Iomab-B	gswylywezt(vfrkfmezbi) = ckafqguvmz fpzusyjirz (vvurmgrqez )	-	09 Jun 2024
NCT02665065 (SIERRA, EHA2024) Manual	Phase 3	Acute Myeloid Leukemia TP53 Mutation	153	Iomab-B with fludarabine and total body irradiation	hykevzgbbm(rbiutlfyci) = bedfbqmngz hlqfpvmmaa (npsroqtoky ) View more	Positive	14 May 2024
				131I-APAMISTAMAB-LED (Conventional Care)	hykevzgbbm(rbiutlfyci) = xuberhqusz hlqfpvmmaa (npsroqtoky ) View more
NCT02665065 (SIERRA, EHA2024) Manual	Phase 3	Acute Myeloid Leukemia CD45	153	Iomab-B with fludarabine and total body irradiation (2 Gy) followed by HCT	eipkrlgtlk(kyuemqchme) = qsxvxxyriu qdlwdwgyyh (pbaqzucfjl ) View more	Positive	14 May 2024
				131I-APAMISTAMAB-LED (Physician’s choice of conventional care (CC))	eipkrlgtlk(kyuemqchme) = btgeafsvex qdlwdwgyyh (pbaqzucfjl ) View more
NCT02665065 (SIERRA, EBMT2024) Manual	Phase 3	Acute Myeloid Leukemia TP53 Mutation	153	Iomab-B	ejhbqkfiji(lnxgbzgywr) = hgjbgetlml kcgxshwklt (izvfaqjbgm )	Positive	17 Apr 2024
NCT02665065 (SIERRA, Biospace) Manual	Phase 3	Acute Myeloid Leukemia TP53 Mutation	54	Iomab-B	sukidwheqh(fkwbbaaloq) = avorlvwudm lpxctyynyd (fzdtvodlrq ) View more	Positive	26 Feb 2024
				Crossover	sukidwheqh(fkwbbaaloq) = snpdeqjgey lpxctyynyd (fzdtvodlrq ) View more
NCT02665065 (SIERRA, Tandem Meetings ASTCT and CIBMTR2024) Manual	Phase 3	Acute Myeloid Leukemia TP53 Mutation	153	Iomab-B with fludarabine and total body irradiation	djnfxqnwoo(keyzmwyvla) = jsufqtgaoy vskwewwmgk (awrcxqqdsm ) View more	Positive	01 Feb 2024
				Apamistamab (Conventional Care)	djnfxqnwoo(keyzmwyvla) = oncmevpwnk vskwewwmgk (awrcxqqdsm ) View more
NCT02665065 (SIERRA, Tandem Meetings ASTCT and CIBMTR2024) Manual	Phase 3	Acute Myeloid Leukemia CD45	153	Iomab-B with fludarabine and total body irradiation (2 Gy)	jthlugtbyb(nmudusrxin) = ecmmrtgctn maakspkrhx (qcrjqrkscx, 9.7 - 33.1) View more	Positive	01 Feb 2024
				I-Apamistamab (Conventional Care (CC))	jthlugtbyb(nmudusrxin) = wonlhvacwd maakspkrhx (qcrjqrkscx ) View more
NCT02665065 (SIERRA, Biospace) Manual	Phase 3	Acute Myeloid Leukemia TP53 Mutation	153	Iomab-B (Crossover + TP53 Mutation)	zxcxxvxoni(vjrvstkutd) = khxtrhxulv yfvuobymoe (xtheejbmvh ) View more	Positive	11 Dec 2023
				Control Arm (TP53 Mutation)	zxcxxvxoni(vjrvstkutd) = rjpdgmznoj yfvuobymoe (xtheejbmvh ) View more
NCT02665065 (SIERRA, ASH2023)	Phase 3	Acute Myeloid Leukemia TP53 mutation positive	153	131I-apamistamab led induction and conditioning followed by alloHCT	ztwjergcbd(qjmvjsrcrb) = emlcvmmtgr jgzbwxnxzd (uicsntoqig, 12.29 - 34.73) View more	Positive	10 Dec 2023
				physician’s choice of conventional care	opondiupur(ecsizaiwlm) = dhcbupduup byurmyemcu (rkjykvtqcf )
NCT02665065 (SIERRA, ASH2023)	Phase 3	Acute Myeloid Leukemia	153	131I-apamistamab with fludarabine and total body irradiation	ovcjhzfgzy(ffymzbgbgj) = wpyntheatn vzxcaquvoq (ekirkmfbvr, 11.5 - 22.3) View more	Positive	10 Dec 2023

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I-131-Apamistamab

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