225Ac-Lintuzumab (225Ac-Actimab-A™, 225Ac-DOTA-huM195, 225Ac-DOTA-Lintuzumab) is the new name of the lead compound developed for the treatment of acute myeloid leukemia (AML). 225Ac-Lintuzumab-A™ is based on a 225Ac-labeled monoclonal antibody targeting CD33, found on myeloid leukemia cells. Lintuzumab (huM195) is the humanized version of the older mouse antibody M195.
AML is the most difficult-to-treat form of leukemia. The majority of patients are older than 60 and most of them do not qualify for the commonly used chemotherapy regimens and their median survival following diagnosis is about 2 months without treatment.
Lintuzumab-A showed to be tolerable at doses less than 4 µCi/kg and demonstrated antileukemia activity. MSKCC is now using doses of 6.4 MBq (175 µCi) per patient. A Phase I/II multi-center AML trial with fractionated doses of Lintuzumab-A was also started, involving 21 patients in Phase I (escalating dose) and 53 patients in Phase II. The completion date is estimated December 2020. Metastatic colon cancer should be the next indication to be explored with this drug through clinical trials.
A new study targeting refractory multiple myeloma patients was also started in December 2016. In June 2018, a new clinical trial to study effect of Actimab-A on minimal residual disease in post-remission AML patients was initiated. Two new clinical studies were initiated in 2019, but start of patient recruitment shifted to 2021, both in combination with Venetoclax, with expected completion in 2022-2024.