We know that immune therapies have just been transformative for many types of cancer, but specifically for kidney cancer they sort of reawaken the immune system. Unfortunately, there’s this tremendous unmet clinical need from patients who receive an immune therapy but it’s not effective, and they receive another standard care, and it’s not effective. So developing new immune therapies, hitting new targets is incredibly important and has not been something that has been particularly successful thus far in kidney cancer.
With that background, there’s an interesting target that comes out of pre-clinical studies called HPK1. It’s essentially a break on T-cells but located within the cell itself. It’s a molecule that basically stops T-cells from becoming activated once it sees its target. So the hypothesis going into this study was we know from pre-clinical work that blocking HPK1 really improves anti-tumour immunity, can help to clear tumours. In a first in human study, if we can pharmacologically inhibit HPK1, would that lead to anti-tumour responses?
What was the methodology and what were the findings?
This was a phase I, first in human study of this molecule NDI-101150, a very selective HPK1 inhibitor. It started with a dose escalation, classic 3+3 design, to find the maximum tolerated dose. Then there was a dose expansion in a few cancer types including kidney cancer, gastric and gastroesophageal tumours, and non-small cell lung cancer.
What we saw was that this was safe, that the toxicity profile was relatively minimal, not high-grade autoimmune effects, manageable GI toxicities. Most notably it really did have single-agent activity, clinical activity, within kidney cancer.
What are the clinical implications of these findings?
The goal is really to see how this might translate into new therapies for patients. We know from the responses within kidney cancer where, in a very refractory setting, after anti-PD-1 therapy, after antiangiogenic therapy, we saw a patient who had a complete response to this therapy – resolution of the tumour – two patients with partial responses, and three patients with stable disease that lasted over six months. In one case a stable disease that lasted for over two years.
The next step is to really examine this in a much larger group of patients. We have the proof of concept, we know that this has a biological plausibility from our preclinical studies and some of our translational work. We know the signals of clinical activity and the signs of safety. Now we need to study this in a much larger group of patients with clear cell kidney cancer, and really determine what are the efficacy parameters.
