Actinium Pharmaceuticals has announced the initiation of patient enrolment in the Phase I study of Iomab-ACT for targeted conditioning before treatment with Memorial Sloan Kettering Cancer Center’s (MSK) CD19 targeted CAR T-cell 19-28z.

A CD45 targeting antibody radiation conjugate, Iomab-ACT is a low dose version of Actinium’s Phase III drug candidate Iomab-B.

It is intended to deplete CD45+ immune cells, such as macrophages, that are implicated in CAR-T related toxicities and could potentially have an anti-tumour effect on chemo-refractory cancers.

The US National Institutes of Health Small Business Technology Transfer grant funding was awarded to Actinium and MSK for carrying out this trial to analyse ARC-based targeted conditioning before CAR-T therapy.

The manufacturing of patient CAR T-cells has begun while patient conditioning with Iomab-ACT followed by 19-28z CAR T-cell infusion is anticipated early in Q2 2021.

Actinium noted that the proof-of-concept data is expected in the second half of this year.

Actinium chief scientific and technology officer Dr Dale Ludwig said: “MSK’s 19-28z CAR T-cell therapy has produced high response rates in patients with relapsed or refractory B-ALL who have previously undergone several lines of standard therapy.

“The ARC technology Iomab-ACT employs enables the delivery of targeted radiation that selective and specifically targets immune cells including those implicated in the CAR-T-associated toxicities of neurotoxicity and cytokine release syndrome.

“We are eager to begin treating patients in this first of its kind pilot study to explore the potential of Iomab-ACT targeted lymphodepletion to modulate the immune system and improve the safety profile of CAR T-cell therapy.”

The scientific rationale for this trial builds on previously reported preclinical data, as well as clinical observations from the SIERRA trial, to justify the combination of MSK’s 19-28z CAR T-cell therapy with Iomab-ACT.