Zanidatamab investigated for HER2+ advanced or metastatic gastro-oesophageal adenocarcinoma
Dr Elena Elimova - The Princess Margaret Hospital, Toronto, Canada
This is a phase II study of zanidatamab combined with standard of care chemotherapy. In this study it involved three standards of care because they vary across Asia and North America and even Europe. So we used CAPOX, FOLFOX and FP, so a combination of zanidatamab and those three chemotherapies, in patients with metastatic or unresectable gastro-oesophageal adenocarcinoma.
What was the study design?
This was a phase II study done in two parts. In the first part we could include patients based on local HER2 testing results. In the second part of the study all HER2 testing results had to be centrally confirmed. It was physician’s choice of chemotherapy and the primary endpoint of the study as it is in most phase II studies was overall response rate. The secondary endpoints included progression free survival and overall survival.
What were the results you were presenting?
It’s a pretty exciting study. The overall response rate was 84% and this study was done at a time where IO was not approved, so this is just zanidatamab with chemotherapy. We saw a duration of response which was meaningful, it was almost 19 months. The progression free survival was also very meaningful, it’s 15 months, and the median overall survival is not yet reached, despite 3.5 years of follow-up. So that was a little bit unexpected but also good news.
What is the safety profile?
The drug is safe. I will tell you that we did have to introduce… the primary issue with the use of this drug is the incidence of diarrhoea. We did have to introduce loperamide prophylaxis probably around halfway through the study. Once loperamide prophylaxis was introduced the incidence of grade 3 diarrhoea went down to 14% so that is quite manageable but this drug does require the use of loperamide.
What are the next steps?
The next steps are already ongoing. The HORIZON-GA phase III study is ongoing. Obviously the results of this phase II study are promising but what you need to make something the new standard of care is a confirmatory phase III study. We hope that that study will finish enrolling at the beginning of next year.
What are your hopes for the long-term clinical impact?
I certainly hope that we’re going to have a new standard of care in my patients. I’m a medical oncologist who treats gastro-oesophageal cancer and I’ll be very honest with you, for a very long time we’ve had very few treatment options in these patients. So, for me, it’s very exciting to see all of a sudden all of these new drugs, including zanidatamab. So I certainly hope it will be the new standard of care but, as we all know, we never know until the phase III study reads out.
