Mast trial protocol update

I've noticed a few others here have reached out to the company to seek clarification around the updated protocol for the IT cohorts, which is what I've done also.

It seemed strange that they were changing from a total viral dose per patient, to a viral concentration per mL. That would effectively give the clinicians a blank cheque so-to-speak, unless a maximum volume per patient was specified.





I did get a response from the company to say that under the new protocol, the volume injected into each tumour varies from 1mL to 4mL depending on tumour size. This allows each tumour which is selected for injection to receive the appropriate dose, up to a maximum of 5 per patient. I asked a follow up question - if the theoretical maximum volume per patient was 20mL (4mL x 5 lesions) or whether there is a maximum volume per patient that is less than 20mL (say 10mL to be split between up to 5 lesions) - but I haven't heard back. But it seems a patient may receive up to 20mL.

I've graphed the total dose for 1mL vs 20mL (the theoretical min and max volume per patient). I know a line graph isn't the correct type for this data set but its easier to visualise than a bar graph. It's a log scale for practical reasons.



The protocol change still doesn't make complete sense to me. The concentration doesn't tell us how much the patients receive. And each patient in a cohort may now receive different total viral dose from one another. But for them to change the protocol, it must mean that the concentration injected into each lesion is more useful information and provides better flexibility in the clinic compared to a set total dose. And a tumours change in size, patients may receive a different total dose at subsequent visits.

We're only just over halfway through the IT cohorts - so long as no safety issues arise and efficacy continues to improve, this trial could have quite some time to go yet. I'm really looking forward to the next trial update.