ESMO 2020 | AMG 160: immunotherapy for mCRPC

So immunotherapy in prostate cancer has been fairly unimpressive to date. Prostate cancer, we recognize as being an immune desert. So by using immunotherapies, such as checkpoint inhibitors, you’re trying to activate immune cells that really aren’t there. So we presented a phase one study of AMG 160, which we consider to be a T-cell recruiting immunotherapy, which can overcome some of the deficiencies involved with checkpoint inhibitors. So AMG 160 is a bi-specific T-cell engager. That means it essentially has two arms: one arm is targeted towards PSMA, represented on prostate cancer cells, and the other arm looks for CD3 looking for T-cells, and tries to engage the two together. It gets the T-cells, the immune cells, right into the prostate cancer and activates them in the presence of prostate cancer. That can lead to a cytokine release, but more relevant is that it can lead to tumor cell lysis. And once one T cell is activated, it can lyse other PSMA expressing cells nearby.

We presented the preliminary results of this phase one study out of the dose exploration portion. So the primary objectives of any phase one study is to determine a safe dose, to determine if it’s tolerable and to determine a recommended phase two dose to move forward with. We presented results from the first 43 patients treated with a data cutoff of July, 2020. We found that AMG 160 was tolerable, that it did have some adverse events and they were predominantly cytokine release syndrome, which is an expected side effect of these sorts of agents.

Cytokine release syndrome can manifest itself as fevers, sometimes some nausea, sometimes some rigors, sometimes some hypotension and some liver transaminitis. We found that the CRS, or the cytokine release syndrome, experienced in our patients on AMG 160 was very manageable with dose mitigation strategies. So some dose mitigation strategies involve starting out with a lower dose as a run in phase, using the steroids as pre-medication for the first cycle or two, and also the use of intravenous fluid prophylactically for possible hypotension.

The main takeaway from our study though, thus far, is the quite exciting efficacy that’s been seen. As I mentioned, immunotherapies in prostate cancer have had very little activity. The PSA response rates for checkpoint inhibitors, whether that be a single or in combination, has been 10% or lower. What we’ve been able to demonstrate in our studies so far, which is still in its dose exploration phase, is that 69% of patients had any PSA reduction and 34% of patients had their PSA dropped by 50% or more. In the 15 patients who had measurable disease by resist criteria, we saw three partial responses; two were confirmed and one was unconfirmed.

Taking all of this together, we see this as very promising data. It’s very exciting to have immunotherapy provide benefits for prostate cancer patients. And our plans are to complete the dose exploration, determine a recommended phase two dose and go into dose expansion. The current phase one study also has a component where AMG 160 is combined with Pembrolizumab. This is based upon preclinical data, which shows AMG 160 induces PD-1, PD-L1 expression within the tumor, and so combining the two would make a lot of sense. Whilst we’ve started that component of the study, these results are not presented here and will be presented at a later date.