Actinium Pharmaceuticals Announces Publication of Actimab-A + CLAG-M Trial Results in Patients with Relapsed or Refractory Acute Myeloid Leukemia in the Peer-Reviewed Journal Leukemia

Rhea-AI Summary

Actinium Pharmaceuticals (NYSE: ATNM) has published results in the journal Leukemia for its Actimab-A + CLAG-M combination therapy trial in relapsed/refractory acute myeloid leukemia (r/r AML) patients. The trial demonstrated significant outcomes including:

• 18.4 months median Overall Survival in patients with 1-2 prior therapy lines
• 75% measurable residual disease negativity (MRD-) across all patients
• Strong efficacy in high-risk patients: 83.3% MRD- in TP53 mutation cases and 100% in prior Venetoclax therapy patients
• 71% of eligible patients received bone marrow transplant with 24.05 months median survival

The company plans to initiate a pivotal Phase 2/3 trial in 2025, comparing Actimab-A + CLAG-M versus CLAG-M alone in r/r AML patients. The treatment showed particular promise for high-risk patients, with results significantly exceeding historical survival rates of 2.4-4.6 months in Venetoclax-failed patients.

Positive

• Significantly improved survival: 18.4 months median OS vs historical 2.4-4.6 months in Venetoclax-failed patients
• High efficacy: 75% MRD-negativity across all patients
• Strong results in hard-to-treat populations: 83.3% MRD- in TP53 mutation cases
• 71% of eligible patients achieved bone marrow transplant with 24.05 months median survival
• FDA alignment secured for pivotal Phase 2/3 trial

Negative

• Phase 2/3 trial yet to begin, indicating lengthy timeline to potential commercialization
• Treatment to specific AML patient subgroups

Insights

Oncology Specialist

The publication of Actimab-A + CLAG-M trial results in Leukemia journal represents a significant clinical breakthrough for relapsed/refractory AML treatment. The 18.4-month median Overall Survival in patients with 1-2 prior therapy lines substantially exceeds historical outcomes with CLAG-M alone (13.3 months).

What's truly remarkable is the efficacy in traditionally treatment-resistant populations. Patients with TP53 mutations (52% of participants) and prior Venetoclax therapy (56%) typically face dismal prognoses, with post-Venetoclax failure patients historically showing only 2.4-4.6 months survival. The achievement of 83.3% MRD negativity in TP53-mutated patients and 100% MRD negativity in prior Venetoclax patients demonstrates Actimab-A's ability to overcome resistance mechanisms that limit conventional therapies.

The therapy's capacity to bridge 71% of eligible patients to bone marrow transplant is particularly significant, as transplant remains the only potentially curative option for r/r AML. The 24.05-month median survival in transplanted patients further validates this approach.

Actimab-A's targeted radiotherapeutic mechanism utilizing Actinium-225 against CD33 appears to provide mutation-agnostic activity - a critical advantage in heterogeneous diseases like AML. With FDA alignment on the pivotal Phase 2/3 trial design, Actinium now has a clear regulatory pathway to potentially transform treatment paradigms for this devastating disease with historically poor outcomes.

Biotechnology Analyst

Actinium's Actimab-A + CLAG-M results publication represents a significant de-risking event for the company's lead program. The superior survival data compared to historical controls positions this combination as potentially practice-changing therapy in the $2+ billion r/r AML market where high-risk patients have few effective options.

The FDA alignment on a pivotal Phase 2/3 trial design is particularly important, signaling regulatory comfort with the development pathway and potentially accelerating time-to-market. The operationally seamless design allows for dose optimization before advancing to the randomized Phase 3 portion, balancing speed with rigor.

Actinium's strategic positioning across multiple AML settings enhances the product's commercial potential. Beyond this r/r AML program, the company's expansion into frontline AML with the triplet combination (Venetoclax + ASTX-727) creates multiple shots on goal. The targeted radiotherapy approach using Actinium-225 represents a differentiated mechanism compared to conventional therapies.

For a company with ~$39 million market cap, successful development of Actimab-A in even one AML indication represents significant upside potential. The mutation-agnostic activity demonstrated across high-risk subgroups suggests broad applicability, and the improved transplant eligibility rates address a critical treatment bottleneck for these patients. The company's focus on the over 100,000 patients with AML and MDS across the US and Europe provides substantial market opportunity if pivotal trials confirm these promising results.

-       Median Overall Survival of 18.4 months with Actimab-A + CLAG-M in patients with relapsed or refractory AML who received 1 or 2 lines of prior therapy

-       Mutation agnostic potential of Actimab-A demonstrated by high rates of Complete Remissions and Measurable Residual Disease Negativity in patients with high-risk features including TP53 mutations and prior Venetoclax treatment

-       Actimab-A + CLAG-M combination yielded deep and clinically meaningful responses with expected and manageable safety profile supporting planned pivotal Phase 2/3 trial

NEW YORK, March 17, 2025 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, today announced that results from the clinical trial evaluating Actimab-A in combination with the chemotherapy CLAG-M in patients with relapsed/refractory acute myeloid leukemia (r/r AML) have been published in the peer-reviewed journal Leukemia. The publication highlights data including long-term survival outcomes from two-year follow-up and better outcomes in high-risk patients. Actimab-A is a novel targeted radiotherapeutic that uses the Actinium-225 (Ac-225) isotope payload directed against CD33, a marker expressed ubiquitously on AML blasts. The trial was conducted at the Medical College of Wisconsin (MCW) which has extensive experience treating relapsed refractory AML patients with CLAG-M.

Actimab-A + CLAG-M Trial Data Highlights from Publication:

• 18.4 month median Overall Survival (OS) in patients who received 1 or 2 lines of prior therapy
• 52% of patients in the Actimab-A +CLAG-M trial had TP53 mutations, 56% had prior allogeneic stem cell transplant and 56% of patients had prior Venetoclax therapy
• Actimab-A + CLAG-M outcomes compare favorably to the results from historical data with CLAG-M alone in the pre-Venetoclax era from MCW's study (median OS of 13.3 months). Typically, patients who have failed Venetoclax treatment demonstrate median survival between 2.4 – 4.6 months as reported in the literature and the patients with a TP53 mutation even have more dismal survival outcomes. Hence this data supports the use of Actimab-A plus CLAG-M for these patients.
• Actimab-A + CLAG-M produced high rates of measurable residual disease negativity (MRD-) including 75% across all patients, 83.3% in patients with a TP53 mutation and 100% in patients with prior Venetoclax therapy
• 71% of eligible patients received a bone marrow transplant (BMT) and median OS in these patients was 24.05 months

Dr. Sameem Abedin, Associate Professor of Medicine at the Medical College of Wisconsin and Principal Investigator of the Actimab-A + CLAG-M study said, "We are delighted that the Actimab-A + CLAG-M results have been published in the peer-reviewed journal Leukemia. Despite advancements in treatment, patients with r/r AML, particularly those with high-risk features including TP53 mutations and prior Venetoclax therapy like those in our study, continue to have dismal outcomes and limited treatment options. We are excited that the combination of Actimab-A and CLAG-M produced high response rates with deep remissions including high rates of MRD negativity, improving access to potentially curable BMT resulting in enhanced survival outcomes. Importantly, we observed that responses were retained in high-risk patients. We believe these results support the utility of targeted radiotherapy for the treatment of AML and its mutation agnostic mechanism of action. We look forward to the initiation of the Phase 2/3 trial of Actimab-A + CLAG-M and further advancing this potentially important therapeutic modality in this patient population with a high unmet need."

Actinium has aligned with the FDA on a pivotal Phase 2/3 operationally seamless trial that will study Actimab-A + CLAG-M in r/r AML patients. The trial will optimize the dose of Actimab-A in combination with CLAG-M, that will be studied in the Phase 3 portion of the trial, which will be a randomized trial comparing overall survival and other outcomes of patients with r/r AML receiving Actimab-A + CLAG-M to CLAG-M alone. The trial is expected to be initiated in 2025.

Sandesh Seth, Actinium's Chairman and CEO, said, "There is significant momentum for Actimab-A with the publication of these positive results in Leukemia and the recent initiation of the frontline AML triplet combination with Venetoclax and the hypomethylating agent ASTX-727 under our NCI CRADA. Actinium is committed to addressing the needs of the over 100,000 patients with AML and MDS in the U.S. and Europe with Actimab-A to realize its multi-billion-dollar market opportunity. Over the course of 2025, we expect to generate additional clinical data further supporting Actimab-A's mutation agnostic, backbone therapy potential for radiation sensitive myeloid malignancies."

About Actinium Pharmaceuticals, Inc.

Actinium is a pioneer in the development of targeted radiotherapies intended to meaningfully improve patient outcomes. Actinium is advancing its lead product candidate Actimab-A, a CD33 targeting therapeutic, as potential backbone therapy in acute myeloid leukemia (AML) and other myeloid malignancies leveraging the mutation agnostic alpha-emitter radioisotope payload Actinium-225 (Ac-225). Actimab-A has demonstrated potential activity in relapsed and refractory acute myeloid leukemia (r/r AML) patients in combination with the chemotherapy CLAG-M including high rates of Complete Remissions (CR) including measurable residual disease (MRD) negativity with improved survival outcomes and is being advanced to a pivotal Phase 2/3 trial. 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. The first clinical trial under the CRADA will evaluate the triplet combination comprised of Actimab-A, Venetoclax (Abbvie/Roche) an oral Bcl-2 inhibitor and ASTX-727 (Taiho Oncology, an Otsuka holdings company) a novel oral hypomethylating agent (HMA) in frontline acute myeloid leukemia (AML) patients. 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 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: https://www.actiniumpharma.com/

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:
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FAQ

What are the survival rates for ATNM's Actimab-A + CLAG-M combination therapy in AML patients?

The trial showed 18.4 months median Overall Survival in patients with 1-2 prior therapy lines, and 24.05 months for patients who received bone marrow transplant.

How effective is ATNM's Actimab-A therapy for high-risk AML patients with TP53 mutations?

The therapy achieved 83.3% measurable residual disease negativity (MRD-) in patients with TP53 mutations, showing strong efficacy in this high-risk group.

What percentage of patients in ATNM's trial achieved bone marrow transplant eligibility?

71% of eligible patients in the trial successfully received a bone marrow transplant (BMT).

When will ATNM begin its Phase 2/3 trial for Actimab-A + CLAG-M therapy?

The pivotal Phase 2/3 trial is expected to be initiated in 2025.

What is the success rate of ATNM's Actimab-A therapy in Venetoclax-treated patients?

The therapy achieved 100% measurable residual disease negativity in patients with prior Venetoclax therapy.