SPEARHEAD-1 is a phase II clinical trial which is an FDA confirmation trial for a T-SPEAR which is a modified T-cell for patients that express both MAGE A4 and who are HLA-A*02. This was based on a phase I clinical trial where we saw durable and prolonged responses within a subset of synovial sarcoma patients. What was presented by Dr D’Angelo was that the confirmatory trial is looking very much like the original phase I trial in terms of durable responses, now complete responses, and the durability of those responses at the same time.
What’s interesting is that outside of that window where patients are getting chemotherapy and their T-cells reinfused, they have a very high quality of life, they’re not coming back and forth for therapy, they’re treating themselves. So this actually, especially within the patients where we had dramatically long responses, now we have a therapy that really gives you the highest quality of life that’s possible because you’re treating yourself.
This is a biomarker-driven single arm study. Given the rarity of the disease and that they both have to not only express a biomarker but have the right HLA so it does take quite a lot of screening to find an appropriate number of patients for this trial. Being that there is nothing that you could randomise this to, this is a first in class, hopefully, trial that will lead to an approval so that we can then add things to it and see if we can improve it.
The key results, once again, are that we have durable prolonged responses, including now two complete responses, and some of these patients are now approaching a year. I think that is something that we do not see in the field of sarcoma where you end up with a durable response that’s prolonged. This seems to be now safe – we’ve lowered the toxicity that came from the original conditioning regimens and so patients are now doing well with the conditioning regimens and they’re doing well with the infusion. There is an association with cytokine release syndrome but that is probably also associated with response.
The next step is to complete accrual to let it read out and hopefully, if we’re very fortunate, we’ll end up with a new modality to treat synovial sarcoma patients that is FDA approved.
This will push overall survival for that subset of patients that respond. So I’m really excited to get to take part in this because it’s really transformative. It’s really important within the synovial community that every patient know their status. So they need to know if they are HLA-A*02 and they need to know if they express one of the tumour antigens that allow for a treatment like this to happen. So this is something where a global screening effort to identify those patients is really needed.