On June 11, 2024 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, reported data from the completed Phase 1b combination trial of Actimab-A + CLAG-M in patients with relapsed or refractory acute myeloid leukemia (r/r AML) at the 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting held June 8 – 11, 2024, in Toronto, Canada (Press release, Actinium Pharmaceuticals, JUN 11, 2024, View Source [SID1234644267]). Actimab-A is an ARC comprised of a CD33 targeting monoclonal antibody conjugated with the alpha-particle emitter Actinium-225 isotope payload. Actimab-A has been studied as a single agent and in combination with chemotherapies and targeted therapies in Phase 1 and Phase 2 trials.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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%
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
(n=17)

53 %

67 %

35 %

TP53+ (n=12)

58 %

80 %

42 %

Ven Failures (n=13)

54 %

100 %

46 %

64% of eligible patients proceeded to bone marrow transplant with these patients having a median overall survival of 24 months.

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.