This is already a hard question because there is not a lot of clinical data. Most of the agents are in preclinical studies and there are several targets under investigation but it’s not clear at this point which will really change the standard of care.
Where do we still see the biggest gaps in evidence for these diseases?
One of the main challenges is in T-cell engager engineering because there has been a lot of progress from the original 1+1 BiTE format to conditional activation design where the drug is masked before it reaches the tumour microenvironment where it’s activated. So these are huge progresses but this comes with huge complexity and some other directions such as TCR T-cell engagers that allow us to target almost every protein in the cell, even intracellular proteins, but they are restricted to the HLAs. So this is also a major limitation. So maybe if we can advance the engineering a bit further and develop multi-HLA drugs this could be a major advancement in the field.
Are there promising ongoing trials that clinicians should be aware of?
I listed the clinical trials, they are all phase I or II. We will still have to wait a bit more to have clinically changing practice trials.
Do you have any key points to take away from your talk?
It’s important to keep in mind that even through all of these steps of development of drugs we have to stay evidence based and not jump too quickly from preclinical to large combination trials because it’s important to really know what’s the clinical utility, what are the good biomarkers, what are the good endpoints when we are testing a new drug.
