Chimeric Therapeutics Ltd (ASX:CHM) has presented "very promising" results of its Phase 1 clinical trial of its chlorotoxin-directed (CLTX) CAR T cell cancer treatment.
The trial of the treatment, which targets progressive glioblastoma, indicates a 75% tumour control rate at the lowest dose, with up to two months of durability.
When the four participants in the trial were treated at the first dose level, three out of the four achieved a best response of stable disease, as assessed by RANO criteria, and the disease control observed was durable for approximately 5–8 weeks.
Data released at SNO meeting
Key additional data was released with the final presentation of two CLTX CAR T abstracts at the Society for Neuro-Oncology (SNO) 26th annual scientific meeting on the weekend.
Abstract CTIM-29, 'Clinical evaluation of chlorotoxin-directed CAR T cells for patients with recurrent glioblastoma' provides insight into the initial clinical data for CLTX while abstract EXTH-10, 'Exploration of a novel toxin-incorporating CAR T cell: how does chlorotoxin recognize glioblastoma cells?' expands on the translational understanding of Chlorotoxin (CLTX) activity.
The clinical data presented in abstract CTIM-29 is from the ongoing CLTX CAR T phase 1 clinical trial in patients with MMP2+ recurrent or progressive glioblastoma.
Tumour recurrence inhibited
The trial demonstrated that tumour recurrence was inhibited at the site of administration of the treatment. Doses of the cells were delivered intratumorally and intraventricularly – meaning they were injected at two sites in the brain, including into the tumours.
MRI scans presented of one patient demonstrated no recurrence of the tumour in the left frontal lobe where CLTX CAR T cells were infused, two months after the CLTX CAR T cell infusion.
Tumour progression was seen only in the left temporal lobe which did not receive the infusion.
This finding suggests that the dual routes of administration (intratumoral and intraventricular) of the CLTX CAR T cells, even at these lower dose levels, may provide additional hope for patients.
“Being able to see tumour control where the CLTX CAR T cells were administered in the brain and tumour progression where they were not administered is very promising – particularly at this low initial dose,” Chimeric’s CEO and managing director Jennifer Chow said.
“That, in addition to the durability of the disease control for up to eight weeks, gives us great reason for optimism as we progress to more active dose levels with dual routes of administration.”
Well tolerated
The administered cells were generally well tolerated with no dose-limiting toxicities and no observed cytokine release syndrome (CRS), an adverse event often associated with CAR T cell therapy.
The company says that a cerebral edema event in one of the patients was only possibly attributed to the CAR T cells – cerebral edema is commonly observed in patients with glioblastoma.
Link to gene expression
The trial also provided early confirmation of the role of the gene MMP-2 in CLTX CAR T tumour recognition and elimination.
Data showed that MMP-2 expression levels increased in parallel with the tumour grade and that CLTX CART T cells preferentially kill tumour target cells with higher MMP-2 expression.
This suggests that CLTX CAR T may be effective even against the most aggressive cancers.
About the clinical trial
The CLTX CAR T Phase 1 clinical trial is underway in California, with plans to expand to a multi-site trial in 2022. The design is a single-arm, open-label trial in patients with MMP2+ recurrent or progressive glioblastoma.
Dose escalation in this trial is planned across four dose levels to a total dose of 440 X 106 CLTX CAR T cells administered by dual intratumoral and intraventricular routes.
The primary endpoints of the trial are to assess the safety of CLTX CAR T cells, determine the maximum tolerated dose schedule and recommend dosage for Phase 2.
Secondary endpoints include bioactivity and efficacy measures.
Melanoma next in line
The positive preclinical evaluation of melanoma augurs well for the next Phase 1 clinical trial.
Early staining of a melanoma cell line confirms another investigative route in those expressing the MMP-2 gene. The company believes this bolsters the case for expanding the clinical development program for CLTX CAR T into additional solid tumours, including melanoma.