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=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.

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P1/2, N=0, Withdrawn, Actinium Pharmaceuticals | N=38 --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 Withdrawn

Combining lintuzumab-Ac225 up to 1.5 µCi/kg with venetoclax in patients with R/R AML has an acceptable clinical safety profile with no mortality at day 30. The MTD, efficacious dose and dosing schedule of lintuzumab-Ac225 in combination with venetoclax is currently investigated in ongoing Phase I Cohort Expansion.

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. Actimab-A at 0.75uCi/kg, combined with CLAG-M is feasible and safe, and this combination demonstrates a high response rate and MRD negativity in a high-risk AML population. Pharmacokinetics at the RP2D indicate rapid drug clearance. Furthermore, responses appear durable, particularly among patients who are able to proceed to alloHCT.

An I-labeled CD45 antibody (Iomab-B [apamistamab-I131]) is currently studied in the registration-type phase 3 SIERRA trial (NCT02665065) for this purpose...Clinical efforts with At-labeled CD45 antibodies and Ac-labeled CD33 antibodies (e.g. Ac-lintuzumab [Actimab-A]) are ongoing. A first anti-AML RIT may soon become available. This might propel further work to develop RIT-based treatments for AML, with many such efforts already ongoing.