Actinium Announces Results of Actimab-A + CLAG-M Combination Trial Highlighted in Oral Presentation at the 2024 Society of Nuclear Medicine & Molecular Imaging Annual Meeting
Actinium Pharmaceuticals (NYSE: ATNM) announced positive results from its Phase 1b trial of the Actimab-A + CLAG-M combination therapy for relapsed or refractory acute myeloid leukemia (r/r AML) at the 2024 Society of Nuclear Medicine & Molecular Imaging Annual Meeting. The study showcased high response rates, bone marrow transplant access, and improved survival outcomes, especially in high-risk patients, including those with TP53 mutations and previous venetoclax treatment. The combination therapy demonstrated no significant safety concerns for major organs and used a validated pharmacokinetic model to estimate biodistribution. The presentation highlighted the dosing, efficacy, and safety profile, with 64% of eligible patients proceeding to bone marrow transplants and median overall survival reaching up to 24 months.
- High overall response rate of 65% in r/r AML patients.
- 75% measurable residual disease negativity.
- 48% one-year overall survival rate across all patient subsets.
- 58% one-year overall survival in high-risk patients.
- 53% one-year overall survival in ELN adverse risk patients.
- 80% measurable residual disease negativity in TP53+ patients.
- 64% of eligible patients proceeded to bone marrow transplant.
- Median overall survival of 24 months for bone marrow transplant recipients.
- No safety signals for major organs such as liver, heart, kidneys, lungs, and intestines.
- Validated pharmacokinetic model used for dosing estimation.
- Only 42% one-year overall survival in high-risk patients.
- 53% one-year overall survival in ELN adverse risk patients.
- data on long-term side effects.
Insights
The results from the Phase 1b trial highlight significant advances in treatment for patients with relapsed or refractory acute myeloid leukemia (r/r AML). AML is a particularly aggressive form of cancer and the inclusion of difficult-to-treat patient subgroups such as those with TP53 mutations and prior venetoclax treatment makes these findings especially noteworthy. The combination of Actimab-A, an antibody radiation conjugate, with the chemotherapy regimen CLAG-M, shows an overall response rate (ORR) of
This suggests that the Actimab-A + CLAG-M regimen could be a potential backbone therapy for high-risk AML patients, offering a new avenue for those who have limited options. Compared to other salvage therapies, these response rates are remarkable and may set a new benchmark for future treatments. However, these results are still early and more extensive Phase 2 and Phase 3 trials will be necessary to validate these findings and assess long-term efficacy and safety.
From a research perspective, the dosimetry results are quite encouraging. The ability to target cancer cells while minimizing harm to surrounding healthy tissues is a critical advancement in radiotherapy. The use of Actinium-225, a powerful alpha-particle emitter, provides a high degree of precision in targeting CD33+ AML blast cells. According to the trial, no safety signals were observed in major organs and the optimal dose was found to be 0.75 µCi/kg. These findings suggest that Actimab-A can deliver effective treatment with a favorable safety profile, potentially transforming the therapeutic landscape for AML.
Moreover, rapid clearance of the radioisotope from the body (undetectable in the blood by 48 hours) reduces the risk of long-term radiation exposure, which can be a significant concern in radio-immunotherapy. This approach could pave the way for subsequent combination therapies, leveraging both targeted and non-targeted methods to improve patient outcomes.
For investors, these clinical results could signify substantial upside potential for Actinium Pharmaceuticals. Positive trial outcomes typically serve as catalysts for stock performance and the high response rates and promising safety data enhance the confidence in Actimab-A's commercial viability. It's essential to consider the broader market implications: the AML treatment market is projected to grow, driven by innovations like targeted radiotherapy. If Actimab-A advances successfully through Phase 2 and Phase 3 trials, it could secure a notable share of this market.
However, early-stage biotech investments come with inherent risks, including the possibility of unforeseen adverse effects in larger patient populations, regulatory challenges and the significant financial burden of late-stage clinical trials. Investors should also keep an eye on the competitive landscape, as other companies are likewise developing advanced treatments for AML. Overall, while the current data is promising, the path to regulatory approval and market entry remains complex and laden with uncertainties.
- Novel targeted radiotherapy-based combination being studied as potential backbone therapy potential relapsed or refractory acute myeloid leukemia
- Actimab-A + CLAG-M produced high rates of response, measurable residual disease negativity, bone marrow transplant access and improved survival outcomes in high-risk patients including TP53+ and venetoclax treated patients
- SNMMI oral presentation highlighted dosimetry results and safety data supporting this novel radiotherapy combination
Sandesh Seth, Actinium's Chairman and CEO, said, "These results demonstrate the immense potential of targeted radiotherapy via ARCs from both an efficacy and safety perspective. Through the use of dosimetry, we can estimate radiation doses to the target organ and non-targeted healthy organs and as observed in this trial, we saw no safety signals for the kidneys, liver or other major organs. Together with the potent efficacy, particularly in these high-risk relapse and refractory patients, we are highly excited by the building clinical profile Actimab-A. We look forward to continuing to advance our Actimab-A program as a broad-based combination approach with targeted and non-targeted therapies in collaboration with the NCI for the benefit of AML patients who are eligible for targeted radiotherapy."
The Phase 1b Actimab-A + CLAG-M combination trial enrolled patients with high-risk r/r AML with the following features:
- Median age of 62 with patients up to 73 years old
91% of patients had intermediate (n=3,13% ) or adverse cytogenetics (n=18,78% )- Over
50% of patients had a TP53 mutation - Median of 2 lines of prior therapy (range:1-5) including:
- Prior bone marrow transplant:
57% - Prior venetoclax treatment:
57%
- Prior bone marrow transplant:
Despite the high-risk profile of the patients on the study, the combination of Actimab-A + CLAG-M produced high rates of response and measurable residual disease negativity and improved survival outcomes across all patient subsets:
Patients | Overall Response Rate | MRD- Rate | 1-year Overall Survival |
All (n=23) | 65 % | 75 % | 48 % |
High-Risk (n=19) | 58 % | 75 % | 42 % |
ELN Adverse Risk | 53 % | 67 % | 35 % |
TP53+ (n=12) | 58 % | 80 % | 42 % |
Ven Failures (n=13) | 54 % | 100 % | 46 % |
Dosimetry and Safety:
- A validated pharmacokinetic model was used to estimate the biodistribution of Actimab-A based on the distribution of CD33+ AML blast cells based on data derived from patients in the Phase 1b study
- Across all dose levels including 0.75 µCi/kg, which was determined to be the optimal dose, and 1.0 µCi/kg (the highest dose in the Phase 1b study) radiation doses for key organs were well below known tolerance levels with external beam radiation therapy (EBRT)
- No safety signals for major organs such as liver, heart, kidneys, lungs and intestines were observed and a safety profile consistent with that expected in heavily pre-treated r/r AML patients given salvage therapy
- A single 30-minute administration of Actimab-A results in rapid radiation delivery and clearance with peak concentration reached around 0.6 hours and undetectable in the blood by 48 hours after administration
- The dose of 0.75 µCi/kg was identified as optimal for this combination therapy and will be further evaluated in the next stage of clinical development
About the SNMMI Annual Meeting
The SNMMI Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The four-day event, taking place each June, provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic.
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 (pre-BLA & MAA (EU)), 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: 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:
investorrelations@actiniumpharma.com
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SOURCE Actinium Pharmaceuticals, Inc.
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