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.

开始日期2021-02-02

申办/合作机构

Memorial Sloan Kettering Cancer Center

NCT02665065 / Active, not recruiting临床3期

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).

开始日期2016-06-01

申办/合作机构

Actinium Pharmaceuticals, Inc.

100 项与 I-131-Apamistamab 相关的临床结果

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100 项与 I-131-Apamistamab 相关的转化医学

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100 项与 I-131-Apamistamab 相关的专利（医药）

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项与 I-131-Apamistamab 相关的文献（医药）

2024-09-19·JOURNAL OF CLINICAL ONCOLOGY

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

Article

作者: Pandit-Taskar, Neeta ; Schuster, Michael ; Litzow, Mark R ; Abboud, Camille ; Lazarus, Hillard M ; Foran, James ; Larkin, Karilyn ; Reddy, Vijay ; Koshy, Nebu ; Jamieson, Katarzyna ; Choe, Hannah ; Haeuber, Elaina ; Sandmaier, Brenda M ; Law, Arjun Datt ; Gyurkocza, Boglarka ; Rowley, Scott D ; Pagel, John M ; Tomlinson, Benjamin ; Seropian, Stuart ; Silverman, Margarida ; McNamara, Kathleen ; MacDougall, James ; Desai, Avinash ; Spross, Jennifer ; Levy, Moshe Y ; Munshi, Pashna ; Sabloff, Mitchell ; Hari, Parameswaran ; Cook, Rachel ; Van Besien, Koen ; Stiff, Patrick ; Kebriaei, Partow ; Orozco, Johnnie J ; 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 ¹³¹I-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 ¹³¹I-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 ¹³¹I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive ¹³¹I-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 (¹³¹I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received ¹³¹I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with ¹³¹I-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 ¹³¹I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the ¹³¹I-apamistamab and conventional care groups, respectively.

CONCLUSION:

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.

2024-01-17·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

作者: Green, Damian J. ; Wilbur, D. Scott ; 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.

2022-05-04·Expert opinion on biological therapy3区 · 医学

Where do we stand with radioimmunotherapy for acute myeloid leukemia?

3区 · 医学

Article

作者: 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.

项与 I-131-Apamistamab 相关的新闻（医药）

2024-11-18

·PRNewswire

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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临床3期财报临床2期放射疗法

2024-09-20

·PRNewswire

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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临床3期临床结果

2024-08-10

·生物制药小编

上市失败后，寻找“接盘侠”

日前，Actinium Pharmaceuticals的核心管线放射性同位素偶联药物（ARC）Iomab-B，针对AML的生物制品许可申请（BLA）被FDA拒绝。在上市申请被拒之后，Actinium公司宣布将为Iomab-B寻找战略合作伙伴，暂时搁置了Iomab-B，并将重点转移到其他管线开发上。新型抗体开发难度高、风险大，同时还伴有监管不确定性。Thermo Fisher聚焦抗体药，铸就全流程新范式，助力创新药开发。备受关注的Iomab-B Iomab-B是CD45靶向药物中研发速度最快的项目，备受业内关注。 Iomab-B由CD45靶向单克隆抗体apamistamab与放射性同位素碘-131偶联而成。CD45是一种广泛表达于所有类型的血液癌细胞和免疫细胞(包括骨髓祖细胞)的抗原，Iomab-B通过apamistamab特异性靶向，实现碘-131精准递送，避免非靶向化疗和/或外部光束辐射对大多数健康组织的副作用，同时有效地杀死患者的癌症和骨髓细胞。 Iomab-B主要被开发作为一种诱导或处理疗法，旨在通过快速耗竭特异性表达CD45的血液癌细胞、免疫细胞和骨髓干细胞，以增加血液肿瘤患者接受骨髓移植（BMT）的机会。BMT能够提高血液肿瘤患者的生存率，但是大多数患者并未能够获得接受BMT的资格，因为BMT需要患者获得疾病缓解。 2023年2月，Actinium公司发布了Iomab-B针对急性髓细胞白血病（AML）的3期临床SIERRA研究的数据，数据显示：22%的患者持续6个月完全缓解（dCR），这种效果在统计学上被认为非常显著；那些达到6个月dCR的患者一年存活率为90%，两年存活率为60%。延伸阅读：ARC药物临床大获全胜，但是？同时，Actinium报告，接受Iomab-B治疗的患者100%能够接受BMT；对照组仅有17%的患者能接受BMT，82%的患者未能够达到持久的完全缓解，没有资格接受BMT。 2023年年底，Actinium向FDA提交了Iomab-B的BLA。被拒原因事实上，Actinium对于Iomab-B的商业化推进十分有信心——从其2022年开始大肆扩招高管团队可以佐证。但，出乎Actinium意料的是，FDA拒绝了Iomab-B用于AML的的BLA申请。根据新闻稿，FDA肯定Iomab-B的主要终点具有统计学意义，但3期SIERRA试验不足以支持Iomab-B的BLA申请。 FDA建议Actinium进行额外的头对头随机临床试验，评估 lomab-B+Flu/TBI 与环磷酰胺+Flu/TBI 预处理后的同种异体BMT，来证明Iomab-B的总体生存期获益。该方案与SIERRA试验不同，SIERRA试验允许医生在对照组中选择挽救疗法和异质预处理方案。此外，拟议的研究方案不允许对照组交叉设计；然而在SIERRA试验中是允许的，同时由于交叉设计，对照组的OS被交叉混淆，而这个OS的次要终点在治疗意向(ITT)人群中没有达到。在Actinium与FDA的讨论中，Actinium打算进一步讨论包括患者群体在内的额外临床试验的细节，FDA建议可能包括所有成年AML患者。寻找“接盘侠” 在同一份新闻稿中，Actinium宣布将在美国寻找Iomab-B的战略合作伙伴，并将未来开发工作重点放在Actimab-A、Iomab-ACT和临床前项目上。虽然不清楚具体原因，但是这表明了Actinium公司认同放弃了对Iomab-B，不过Actinium公司在Iomab-B的开发上投入了大量心血。有可能是FDA对Iomab-B提出的头对头研究，也有可能是因为Iomab-B后续开发的资金缺口。根据Actinium发布的2024年第二季度财报，该公司的现金、现金等价物和限制性现金为8635.5万美元。 Actimab-A是一款CD33靶向的、基于锕-225的放射性同位素偶联药物（ARC），旨在与其他方案联合应用，开发一种AML骨干疗法。目前，Actimab-A正在进行2项1/2期研究，分别是Actimab-A+CLAG-M联用治疗AML，和Actimab-A+Venetoclax联用治疗AML。 Iomab-ACT与Iomab-B相似，但是由CD45单抗apamistamab与较低水平的非清髓性碘-131偶联而成，作为CAR-T等细胞或基因治疗前的预处理开发。目前处于临床开发阶段。小结最近，核药很火，多笔大额投资、并购和交易。相较于传统的放射疗法，放射性偶联药物能够实现特异性给药，能够提高潜在疗效，并且降低治疗副作用，减少对健康细胞的伤害。参考资料： 1.https://www.biospace.com/drug-development/actinium-to-farm-out-aml-radioactive-drug-after-fda-asks-for-another-trial 2.https://ir.actiniumpharma.com/press-releases/detail/486/actinium-provides-regulatory-update-on-planned-bla-filing

临床3期临床结果免疫疗法快速通道临床成功

100 项与 I-131-Apamistamab 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
难治性急性髓细胞白血病	临床3期	美国	Actinium Pharmaceuticals, Inc.	2016-06-01
难治性急性髓细胞白血病	临床3期	加拿大	Actinium Pharmaceuticals, Inc.	2016-06-01
复发性急性髓细胞白血病	临床3期	美国	Actinium Pharmaceuticals, Inc.	2016-06-01
复发性急性髓细胞白血病	临床3期	加拿大	Actinium Pharmaceuticals, Inc.	2016-06-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


SNMMI2024	N/A	-	-	Iomab-B	鏇築醖衊簾鏇淵衊壓壓(獵鬱製淵顧鑰顧廠餘築) = 築憲繭醖鏇獵積蓋製夢願蓋糧簾齋鏇醖憲積廠 (繭鹹齋鹽獵範襯願餘壓 )	-	2024-06-09
NCT02665065 (SIERRA, EHA2024) 人工标引	临床3期	急性髓性白血病 CD45	153	Iomab-B with fludarabine and total body irradiation (2 Gy) followed by HCT	(醖網膚鑰鏇膚範艱遞簾) = 齋廠選簾鏇積齋鏇窪餘廠窪範膚遞鹹餘積簾簾 (窪蓋觸鑰鹽襯簾壓構獵 ) 更多	积极	2024-05-14
				131I-APAMISTAMAB-LED (Physician’s choice of conventional care (CC))	(醖網膚鑰鏇膚範艱遞簾) = 遞窪壓襯膚製憲艱齋築廠窪範膚遞鹹餘積簾簾 (窪蓋觸鑰鹽襯簾壓構獵 ) 更多
NCT02665065 (SIERRA, EHA2024) 人工标引	临床3期	急性髓性白血病 TP53 Mutation	153	Iomab-B with fludarabine and total body irradiation	壓憲顧壓鹹淵獵鏇餘淵(餘艱構餘製鹹鏇遞膚蓋) = 壓餘齋淵鹹積艱獵鑰醖網構糧鑰憲鬱積鏇窪齋 (壓廠構醖積繭願選範獵 ) 更多	积极	2024-05-14
				131I-APAMISTAMAB-LED (Conventional Care)	壓憲顧壓鹹淵獵鏇餘淵(餘艱構餘製鹹鏇遞膚蓋) = 醖觸鬱選齋範構願淵鏇網構糧鑰憲鬱積鏇窪齋 (壓廠構醖積繭願選範獵 ) 更多
NCT02665065 (SIERRA, EBMT2024) 人工标引	临床3期	急性髓性白血病 TP53 Mutation	153	Iomab-B	襯網廠淵鏇醖製艱壓選(製構範齋獵齋衊鑰鏇糧) = 齋衊廠簾窪廠簾簾繭鏇衊壓餘鬱網鏇繭膚鑰窪 (構鹹艱膚鏇壓襯鬱壓艱 )	积极	2024-04-17
NCT02665065 (SIERRA, Biospace) 人工标引	临床3期	急性髓性白血病 TP53 Mutation	54	Iomab-B	壓願窪齋壓鬱繭鑰繭簾(選鹹製夢鏇淵觸製憲壓) = 遞顧鹹範鹽醖膚製餘選顧鏇淵鹹鏇積獵製糧鏇 (廠衊願遞餘鏇觸觸選窪 ) 更多	积极	2024-02-26
				Crossover	壓願窪齋壓鬱繭鑰繭簾(選鹹製夢鏇淵觸製憲壓) = 選膚鹽積餘鬱鑰鑰遞糧顧鏇淵鹹鏇積獵製糧鏇 (廠衊願遞餘鏇觸觸選窪 ) 更多
NCT02665065 (SIERRA, Tandem Meetings ASTCT and CIBMTR2024) 人工标引	临床3期	急性髓性白血病 CD45	153	Iomab-B with fludarabine and total body irradiation (2 Gy)	衊鹹築廠遞築遞憲衊網(餘廠鑰艱繭鬱繭鑰選鏇) = 繭醖壓範壓繭積襯觸糧顧網鬱鹹簾蓋鏇鏇製獵 (積醖窪簾餘遞窪蓋蓋餘, 9.7 ~ 33.1) 更多	积极	2024-02-01
				I-Apamistamab (Conventional Care (CC))	衊鹹築廠遞築遞憲衊網(餘廠鑰艱繭鬱繭鑰選鏇) = 願鑰積構築鏇憲製蓋醖顧網鬱鹹簾蓋鏇鏇製獵 (積醖窪簾餘遞窪蓋蓋餘 ) 更多
NCT02665065 (SIERRA, Tandem Meetings ASTCT and CIBMTR2024) 人工标引	临床3期	急性髓性白血病 TP53 Mutation	153	Iomab-B with fludarabine and total body irradiation	衊獵齋窪繭鹹獵醖遞鑰(夢淵顧糧醖蓋願齋壓網) = 鑰鬱窪廠簾鏇積鬱選鏇觸壓簾糧膚艱夢範繭築 (鑰顧窪夢膚憲簾範鏇餘 ) 更多	积极	2024-02-01
				Apamistamab (Conventional Care)	衊獵齋窪繭鹹獵醖遞鑰(夢淵顧糧醖蓋願齋壓網) = 齋齋鏇襯範醖鏇鬱遞憲觸壓簾糧膚艱夢範繭築 (鑰顧窪夢膚憲簾範鏇餘 ) 更多
SIERRA (Biospace) 人工标引	临床3期	急性髓性白血病 TP53 Mutation	153	Iomab-B (Crossover + TP53 Mutation)	築願簾範襯鏇鬱淵艱願(願壓築願蓋範鑰選鹹窪) = 衊鬱壓獵膚獵餘糧膚窪網齋壓鏇顧憲廠壓艱鏇 (餘糧衊範積廠廠醖選築 ) 更多	积极	2023-12-11
				Control Arm (TP53 Mutation)	築願簾範襯鏇鬱淵艱願(願壓築願蓋範鑰選鹹窪) = 製網網積願範衊鬱膚鑰網齋壓鏇顧憲廠壓艱鏇 (餘糧衊範積廠廠醖選築 ) 更多
NCT02665065 (SIERRA, ASH2023)	临床3期	-	153	131I-apamistamab with fludarabine and total body irradiation	(鬱壓遞夢壓醖鹽鏇蓋衊) = 遞齋鹽膚壓襯窪獵遞廠鹹鹹鏇積蓋顧築觸衊壓 (鹽製壓壓廠範艱製鬱顧, 11.5 ~ 22.3) 更多	积极	2023-12-10
NCT02665065 (SIERRA, ASH2023)	临床3期	-	153	I-apamistamab led induction and conditioning followed by alloHCT	築積網繭簾膚淵繭構艱(觸壓齋遞蓋蓋壓鏇鑰願) = 夢襯壓選襯淵遞選範餘鏇範願繭繭膚網觸積鹹 (鹽壓繭觸夢艱壓壓鹹膚, 12.29 ~ 34.73)	积极	2023-12-09