On December 14, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs reported that data from the Phase 1 portion of its Actimab-A and venetoclax combination trial in patients with relapsed or refractory acute myeloid leukemia (AML) was presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH) (Free ASH Whitepaper) that is being held December 11 – 14, 2021 in Atlanta, Georgia and virtually (Press release, Actinium Pharmaceuticals, DEC 14, 2021, View Source [SID1234597105]).

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Patients enrolled in the study to date have been a median age of 64, with 75% of patients having adverse cytogenetics and 50% of patients having received and failed prior venetoclax and hypomethylating agent (HMA) therapy. The trial will continue to dose escalate to a fourth dose cohort of 1.5 μCi/kg to determine the dose for the Phase 2 portion of the study. Key findings from the study to date include:

67% overall response rate (ORR) with 2 remissions in patients with a TP53 mutation
One patient achieving remission has been on study for over 230 days and remains in follow-up after previously failing venetoclax HMA therapy before enrolling on Actimab-A study
No early mortality (< 30 days) in the study to date
"Venetoclax has become a staple therapy for patients with AML, however, patients with relapsed or refractory disease continue to represent a major unmet medical need with median overall survival reported to be 5.5 months and only 3 months in patients that do not respond to venetoclax therapy. After confirming a mechanistic synergy between Actimab-A and venetoclax, we were eager to begin this combination clinical trial. This initial data is highly encouraging thus far, particularly the 2 remissions in patients with a TP53 mutation, which is associated with very poor clinical outcomes. These data support advancing to the Phase 2 portion of the study and based on the high response rates in TP53 patients, we will actively explore a development strategy with this patient population. We look forward to completing the Phase 1 dose escalation portion of this study, to determine the recommended Phase 2 dose so we can continue to advance this novel combination given the high unmet need of the patient population," said Avinash Desai, Actinium’s Chief Medical Officer.

Venetoclax is a targeted therapy for patients with AML that targets Bcl-2, a protein that is overexpressed in certain cancers that enables cancer cells to evade apoptosis or programmed cell death. Actinium evaluated this novel combination after identifying that Actimab-A, via its targeted radiotherapy mechanism, could deplete Mcl-1, a protein that is upregulated in refractory AML cells and mediates resistance to venetoclax. In preclinical studies, Actinium showed that Actimab-A combined with venetoclax, resulted in greater AML cell killing than either Actimab-A or venetoclax alone and resulted in enhanced tumor regression and survival in venetoclax-resistance AML tumor models. The Phase 1/2 trial is a multi-center clinical trial that will enroll up to 38 patients with the Phase 2 portion of the trial to evaluate for safety, minimal residual disease status, disease free survival and overall survival.

Source:

Tenold et al. (2021) Outcomes of Adults with Relapsed/Refractory Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents at a Comprehensive Cancer Center. Front. Oncol. 11:649209. doi: 10.3389/fonc.2021.649209