Actinium Pharmaceuticals Inc (ATNM)

[GoodGuyBill]

https://ash.confex.com/ash/2019/webprogram/Paper128838.html

Results

From these data, a significant but transient decrease in lymphocytes and white blood cells was observed compared to pre-DI values. An 85% decrease of lymphocytes was observed at the post-DI time point, a 67% decrease at day 1 post-DI, and a 43% decrease at the time of therapeutic infusion. Peripheral blasts were also transiently decreased at the post-DI time point (35%), indicating that low dose Iomab-B may exert an anti-tumor effect in these patients. Interestingly, the levels of platelets, hematocrit, and neutrophils were unchanged at the Pre-TI time point compared to Pre-DI, reflecting the comparatively lower surface antigen levels of CD45 on these cell types. In addition, data from a subset of treated patients (n=25) was used to calculate the radiation absorbed dose to bone marrow to determine an appropriate amount of Iomab-B that would not impart more than 2 Gy, a threshold that is considered to be non-myeloablative. This analysis determined that 75 mCi Iomab-B could be administered as a non-myeloablative amount and has been proposed as the starting dose for a clinical trial using Iomab-B for targeted lymphodepletion prior to CAR-T. Additional calculations were performed to model the clearance of Iomab-B to determine at what time post-infusion a CAR-T could be administered without the amount of residual radiation to bone marrow exceeding a safe level (0.25 Gy). Based on clinical data from the SIERRA trial, the average effective half-time of Iomab-B was 45.1 hours and the time frame for CAR-T administration following 75 mCi of Iomab-B was 136 hours (5.7 days). Given that administration of radiopharmaceuticals often requires special safety precautions, the proposed range of doses for Iomab-B is considered an outpatient infusion without the need for isolation.

Conclusions

Despite the importance of lymphodepletion prior to adoptive cell therapies, there has been very little optimization of this step. Clinical data collected using a low dose of Iomab-B for dosimetry has demonstrated that this method of lymphodepletion is specifically targeted to CD45+ immune cells, may have an anti-tumor effect, and can be administered in an outpatient setting. These clinical and logistical attributes are attractive characteristics for lymphodepletion and supportive of using Iomab-B as a novel lymphodepletion regimen prior to adoptive cell therapies such as CAR-T.