Phase I Study Findings: anitocabtagene autoleucel for RRMM treatment | Binod Dhakal, MD | EHA 2024

Hi, my name is Bino Dhakal and I'm associate professor of medicine at Medical College of Wisconsin. At this IHA meeting, I'm presenting an oral abstract on the phase one study of CAR-T-DDBCMA in patients with relapsed refractory multiple myeloma, results from at least one year follow-up in all patients. CAR-T-DDBCMA has been named anitocaptase in autolysel or anitocell. This is a unique CAR-T, a noble CAR-T with, because the binding domain is a synthetic binding domain called a D-domain. D-domains are triple alpha helical structure with a hydrophobic core. And this domain allows high transduction efficiency and high surface density on the surface of a car cell. Additionally, there is a low risk of tonic signaling because of the small size and lack of side chains. We tested this anitocell in patients in a dose escalation first in human phase one study. Two dose levels were tested, dose level one and dose level two. And based on the early data, the decision was made to expand dose level one, which is a median dose of 115 million cells. The patients who were included had a triple class exposure, means exposed to three different class of drugs and had to have three different lines of therapy or they need to be triple class refractory. In the baseline characteristics, the median age was 66 years, the median prior lines of therapy was four and 100% of patients were triple class refractory patients. In addition, we define what we call as a high risk prognostic feature defined as bone marrow plasma cells are more than 60%, ISS stage three disease and extra<|tr|>mary disease. 63% of patients had at least one of those features. More importantly, the true extra medullary disease was present in 34% of the patients because the study allowed patients with non-measurable disease but with measurable plasma cytoma to be included. The overall response rate was 100% in this total patient population. The complete response rates and better was 76% and 92% of the patients achieved very good partial response rates and better. The most impressive is the complete response rates and better was similar in patients with high risk prognostic feature, extra medullary disease, high risk cytogenetics with and without one Q gain and age more than 65 years. At a median follow-up of 26.5 months, the median PFS was not reached with anitocell. The median PFS in patients with complete response and better was also not reached. The 24-month PFS rate was 56%. There could be further evolution in the curve with additional follow-up but the median PFS is likely to be greater than two years in this very difficult to treat patients. In the extra medullary disease, at a follow-up of 33 months, the median PFS was not reached and that is quite impressive. In 24-month PFS was more than 55% in the overall patient population and different subgroups including the high risk subgroups and that is perhaps the highest PFS rates reported at 24 months in this difficult to treat patients. In terms of safety, there are no new safety signals. The grades 3 and CRS was not present in patient with those level 1 and there was only one case of grade 3 ICANs. There were no delayed neurotoxicities, there were no Parkinson's like syndromes, there were no granulopalysis and no Guillain-Barré syndrome. So in conclusion, Ineutrocell is a noble CAR T construct based on its noble binding domain and with the attributes of high transduction efficiency and high surface expression of the CAR. These attributes have enabled the clinical activity what we saw in phase 1 with 100% response rate and 76% of patients achieved complete response rates and better. At 26.5-month follow-up, the median PFS was not reached in the entire patient population and also in the high risk subgroups. In terms of safety, this efficacy is paired with a manageable safety profile with lower risk of high grade CRS ICANs and no delayed neurotoxicities. This study is, this product is being evaluated right now in a single phase 2 pivotal study in patients with 3 or more prior lines of therapy and is undergoing, enrolling the patients. Thank you.