Elicera Therapeutics announced today that its novel CAR T-cell therapy, ELC-301, has successfully eliminated all active lymphoma in two out of three patients treated in the first cohort of its ongoing Phase I/IIa CARMA study. These preliminary results will be presented at the Swedish Cancer Research Meeting (SCRM) in Malmö, Sweden.
The patients in this initial cohort received the lowest planned dose level, equivalent to just one-tenth of the maximum dose intended for the study. Despite this conservative dosing approach, two patients achieved complete metabolic response, meaning no active lymphoma was detected on specialized scans.
"We are thrilled with the early results from the CARMA study, where ELC-301 has successfully cleared all active lymphoma in two out of three treated patients, including one who had previously failed CD19 CAR T-cell therapy," said Jamal El-Mosleh, CEO of Elicera Therapeutics. "This was achieved despite using a low dose in a challenging patient population."
Patient Outcomes in Detail
The first patient achieved complete metabolic response at the one-month assessment, with the response maintained through the six-month follow-up. The third patient, who had previously been treated with standard CD19 CAR T therapy, also achieved complete metabolic response at the one-month follow-up.
The second patient, who had also received prior CD19 CAR T-cell therapy, showed possible disease progression at the three-month follow-up, though this is still to be confirmed.
These results are particularly significant given that the study is targeting patients with relapsed or refractory B-cell lymphoma, a population that typically has limited treatment options after failing standard therapies.
The iTANK Platform: Enhancing CAR T-Cell Therapy
ELC-301 is distinguished by its incorporation of Elicera's proprietary iTANK platform, which arms CAR T-cells with additional immune-activating properties. The technology involves incorporating a transgene into CAR T-cells that encodes a neutrophil activating bacterial protein (NAP).
This modification enables the CAR T-cells to not only directly target cancer cells expressing the CD20 antigen but also to activate a broader immune response against the tumor. The NAP secreted from the CAR T-cells enhances their function and activates a parallel bystander immune response via CD8+ killer T-cells.
This approach is designed to address two major challenges in CAR T-cell therapy: the diverse range of tumor antigen targets and the hostile tumor microenvironment that often limits effectiveness.
CARMA Study Progression
The CARMA study is continuing with patient enrollment at escalating dose levels. Cohort 2 has already been initiated, with two patients treated so far at a dose level three times higher than that used in Cohort 1.
The study is structured with a dose-escalation phase (Phase I) and a dose-expansion phase (Phase IIa). Phase I aims to establish the optimal dose and safety profile in up to 12 patients across three cohorts, while Phase IIa will further evaluate the efficacy of the maximum tolerated dose in an additional six patients.
"These preliminary data, though from a small cohort, highlight the unique potential of our iTANK-armed CAR T-cell therapy and support our belief that ELC-301 may offer meaningful benefits where existing therapies fall short," added El-Mosleh.
The CARMA study is being conducted at Uppsala University Hospital and Karolinska University Hospital in Huddinge, Sweden. Additional preliminary data from subsequent cohorts will be reported as the study progresses and in connection with presentations at scientific conferences.
About ELC-301 and CAR T-Cell Therapy
ELC-301 is classified as a fourth-generation CAR T-cell therapy targeting the CD20 antigen, which is commonly expressed on B-cell lymphomas. CAR T-cell therapies involve genetically modifying a patient's own T-cells to express a chimeric antigen receptor (CAR) that targets specific molecules on cancer cells.
While CAR T-cell therapies have shown remarkable success in certain blood cancers, they face challenges in treating solid tumors and in patients who relapse after initial treatment. Elicera's approach with the iTANK platform aims to overcome these limitations by enhancing the CAR T-cells' ability to trigger a broader immune response.
The technology has shown promise in preclinical studies, with proof-of-concept data published in Nature Biomedical Engineering in April 2022. The publication demonstrated that CAR T-cells expressing the bacterial virulence factor could trigger potent bystander antitumor responses in solid cancers.
As the CARMA study progresses through its dose-escalation phase, the medical and scientific communities will be watching closely to see if these early promising results are maintained at higher doses and in more patients, potentially offering new hope for patients with relapsed or refractory B-cell lymphoma.
