Thanks for pulling those together, and not sure if you've seen it yet but here is a useful poster of our phase 1 trial which is quite useful (explains the method i.e. surgery, and the CAR-T, as well as the dual therapy from cohort 2 onwards (i.e. cohort one is only at the tumor site intertumoral, where as cohort 2, 3 and 4 are both intertumoral and intraventricular (cavity in the brain).
So what patient UPN 487 experienced appears to be a disease stabiilisation at the intertumoral catheter site.. but a distant recurrence which was MMP2+. What they mean by dual therapy is that this patient was likely enrolled into the cohort 2 which had both intertumoral and intraventricular catheter sites. The significance of this has been talked about before, but I'll reiterate again below.
I'm going to link a NEJM journal which shows the first time a intraventricular CAR-T was used for GBM (targeting IL13Ra2, licenced to Mustang Bio), which was done at the City of Hope, and you guessed it.. the same team running our trial. NEJM CAR-T City of Hope IL13Ra2
The above mentioned patient, Dr Richard Grady, was the first ever patient (and as far as I'm concerned, the only one ever) to have had a complete response from multiforme GBM. He was dosed with a low dose of the IL13Ra2 CAR-T for several weeks, which like our trial thus far, saw disease stabllisation at the intertumoral catheter site, but had recurrence in several places in the brain as well as his spine. Like our CLTX CAR-T, it was unable to stop distant recurrence.
That is when the team at City of Hope, for the first time ever, tried an intraventricular catheter site for the CAR-T (the cavity in the brain is filled with fluid that circulates the rest of the brain and down the spinal cord). And what happened next was incredible to say the lease. All tumors literally melted away within several weeks of starting the intraventricular catheter injections, at the low dose.
This is why cohort 2 is going to be one to really watch out for because it should in theory be able to reach distant tumors and destroy tumors within the brain and even the spine. Our Cohort 2 will double the low dose as well as having both catheter sites.
Still early days, but we are generating amazing data at such an early stage of this trial.. with cohort 3 starting early 2022 in 3 trial sites, it's looking like they may return to the SNO next year showing how this trial progressed from cohort 1 through to cohort 3... with possibly a basket trial cohort 1 using CLTX and the CDH-17 CAR-T... a lot to look forward to in 2022
Anyway it looks like they'll have some more details to announce at the AGM on our first four patients... looking forward to getting that update tomorrow.
Goodluck all
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