AMG 160: A PSMA-targeted, bispecific T-cell engager immune therapy for mCRPC

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Published: 22 Sep 2020
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Dr Ben Tran - Peter MacCallum Cancer Centre, Melbourne, Australia

Dr Ben Tran spoke to ecancer online about AMG 160 presented at the ESMO 2020 Virtual Congress.

He initially outlined the mechanism of AMG 160 and why there is a need for these types of immune therapies.

Dr Tran went into detail regarding the toxicities for AMG 160, which revolved around the management of cytokine release syndrome.

Dr Tran wrapped up with their expectations for the future of this work, and the potential place AMG 160 could sit in the treatment landscape of mCRPC.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

There have been significant advances in the treatment of metastatic castration resistant prostate cancer over the past many years, however, the role of immunotherapy remains to be determined. Many immunotherapies have been trialled in prostate cancer, in particular the checkpoint inhibitors, with very disappointing results. So there really is a need to utilise the potential benefits of immunotherapy and the long-term benefits of immunotherapy as seen in other cancers in that of metastatic castration resistant prostate cancer.

The phase I study I presented at ESMO 2020 is that of an agent called AMG 160. AMG 160 is considered a T-cell recruiting immunotherapy but more specifically it is a bispecific T-cell engager. Bispecific T-cell engagers, as their name entails, have two arms. One arm targets T-cells and recruits T-cells towards the prostate cancer immune microenvironment and the other arm targets prostate cancer itself, targeting the PSMA which is a known and validated target for both the imaging and treatment of prostate cancer.

The study we presented is a phase I study of AMG 160 in patients with metastatic castration resistant prostate cancer. These are preliminary results that have been discussed at ESMO, we presented the results from the first 43 patients treated on this study, all from the dose exploration part of the study. As with any phase I study the major aims are to determine safety and to determine the recommended phase II dose. We also have secondary endpoints of evaluating preliminary evidence of efficacy.

The phase I study is made up of three components, one is the dose exploration component which are the preliminary results I’ll be presenting. There is a dose expansion cohort where we’re treating larger numbers of patients at the recommended phase II dose and there’s also a component where AMG 160 is combined with pembrolizumab. This is based upon preclinical data that suggests that using AMG 160 upregulates PD-1/PD-L1 and hence the combination with a PD-1 inhibitor such as pembrolizumab would make sense. Whilst that component of the study has been started, those results will not be presented and have not been presented at ESMO 2020.

The results that I did present are, as I said, of the first 43 patients treated on the study. All patients received at least one dose of AMG 160. There were some side effects seen, although it was largely a tolerable treatment. The major side effect seen was that of cytokine release syndrome. This is something that’s expected with this class of treatment. Cytokine release syndrome can result in patients experiencing fevers and sometimes there are chills or rigours. This can lead to transaminitis as well as hypotension and some nausea and vomiting and diarrhoea in some patients.

As the doses increased the incidence of CRS has increased however the study has used mitigation strategies to reduce the incidence of CRS. These mitigation strategies have included a lower priming lead-in dose before the target dose is achieved, the use of steroid premedication and also the use of prophylactic intravenous hydration to prevent issues of hypotension. As I mentioned, the CRS is predominantly hypotension and transaminitis. The transaminitis itself was usually self-limiting and resolved within 1-3 days.

We did see very exciting preliminary evidence of efficacy with the AMG 160 patient population. 69% of patients had a reduction in PSA with 34% of patients having their PSA drop by 50% or more. This is particularly impressive given that as a phase I study the patient population is heavily pre-treated with 60% of patients having four or more prior lines of therapy coming into this study. Of the 43 patients treated, 15 patients were evaluable for RECIST responses and, of that, three out of 15 had a partial response and two of those are confirmed and one is unconfirmed.

So overall we’re very excited about AMG 160. Even though it’s very early days into development of this agent and even though we’re still completing our phase I dose exploration portion and still trying to determine our recommended phase II dose, the fact that the toxicity is manageable and the fact that the efficacy is better than seen with any other prior immunotherapy in prostate cancer is very exciting. We hope to achieve our recommended phase II dose soon and begin the dose expansion portion of the study. There are not yet any plans for future further development, although talks are still ongoing about how best to place AMG 160 in the treatment landscape for mCRPC.