Actimab-A (lintuzumab-Ac225)

The composite complete remission (CRc) rates (CR/CRi) were 56.6% overall, 50% in patients with mutated TP53, and 38.5% in prior venetoclax-treated patients. Among all patients (n = 26), estimated 2-year OS was 23.1% (95% CI, 9.4-40.3) and estimated 1-year PFS was 30.8% (95% CI, 14.6-48.5). Lintuzumab-Ac225 plus CLAG-M was well tolerated with expected, manageable toxicities, while yielding deep and meaningful responses in high-risk R/R AML patients.

P1, N=48, Not yet recruiting, National Cancer Institute (NCI)

P1, N=26, Completed, Medical College of Wisconsin | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> May 2024

P1, N=26, Active, not recruiting, Medical College of Wisconsin

P1, N=26, Active, not recruiting, Medical College of Wisconsin | Trial primary completion date: Oct 2024 --> May 2024

The combination of lintuzumab-Ac225 and venetoclax had a manageable safety profile and no early mortality at day 30. The MTD was not reached and no significant toxicities have been reported during the follow-up period. Modified dosing schedule in Cohort 4 of the combination demonstrated improved anti-leukemic effects.

We have demonstrated promising therapeutic responses with Actimab-A (lintuzumab- Ac225, an anti-CD33 antibody conjugated with actinium-225) in patients with AML, including in combination trials with chemotherapy regimen CLAG-M and targeted therapy venetoclax...Objective: In this study, we evaluated the antileukemic activity of lintuzumab-Ac225 in FLT3 mutant AML as a single agent and in combination with the FLT3- targeted inhibitor gilteritinib... Our findings show that single-agent lintuzumab-Ac225 has potent antileukemic activity against FLT3 mutant AML and can significantly improve the effect of FLT3 inhibitors in combination. Based on these results, lintuzumab-Ac225 may potentially provide new combination therapy for patients with FLT3 mutant AML.

Induction consisted of G-CSF, 300mcg/d, given D1-6, cladribine 5mg/m2, given D2-6, cytarabine 2g/m2, given D2-6, and mitoxantrone 10mg/m2, given D2-4. CLAG-M followed by Lintuzumab-Ac225 yielded significantly better clinical outcomes in high-risk populations, particularly in patients previously treated with venetoclax combinations. The results further support the late-stage clinical development of Lintuzumab-Ac225 in combination with CLAG-M in R/R AML.

P1/2, N=38, Recruiting, Actinium Pharmaceuticals | Trial completion date: Jan 2023 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Nov 2023

P1/2, N=0, Withdrawn, Actinium Pharmaceuticals | N=38 --> 0 | Not yet recruiting --> Withdrawn

In this study, we demonstrate CD33 ARC alpha targeted radiotherapy depletes human CD33 positive immune suppressing MDSCs present in multiple cancer types, to enhance antitumor immunity. These findings present a translatable strategy that supports further evaluation of 225Ac lintuzumab as a MDSC targeting agent to improve the efficacy of antitumor therapies.