Combination of MEDI0680, an anti-PD-1 antibody, with durvalumab, an anti-PD-L1 antibody:

Share :
Published: 12 Oct 2016
Views: 3333
Dr Omid Hamid - The Angeles Clinic, California, USA

Dr Hamid speaks with ecancertv at ESMO 2016 about the outcomes of a phase I study into the responses to combined PD-1 and PD-L1 inhibition in multiple tumour sites.

PD-1 and PD-L1 have been targets of immune checkpoint inhibitor therapy independently across multiple cancer types and sites, and Dr Hamid describes the initial results of co-targeting both at once.

He introduces upcoming phase II trials in bladder cancer, and considers how to improve patient responses for those expressing either high or low levels of the biomarkers.

ecancer's filming at ESMO 2016 has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.


ESMO 2016

Combination of MEDI0680, an anti-PD-1 antibody, with durvalumab, an anti-PD-L1 antibody

Dr Omid Hamid - The Angeles Clinic, California, USA

At this year’s meeting I’m presenting data from a phase I study of the combination of an anti-PD1 inhibitor, MEDI0680, and an anti-PD-L1 inhibitor, durvalumab, in patients with all types of cancer. What we’ve seen is great single agent activity with PD1 inhibitors and similarly with PD-L1 inhibitors. There’s some data showing that you can get a greater inhibition of that pathway with dual inhibitor approach. There’s also some preclinical data showing that the way that tumours progress through PD1 blockade is up-regulation of CD80 which then interacts with PD-L1 and can be an escape from response.

What are the phase one results?

We saw some promising results in this study. There was one complete response and eight partial responses for an 18% response rate. What we’ve seen in this study is that dosing every two weeks with both drugs we have seen only two grade 3 adverse events, a QT prolongation and a transaminitis, no grade 4 or grade 5. There are patients with ongoing response, eight out of the nine patients are ongoing responders. These drugs are both dosed every two weeks for one year and patients are on the study past one year so we’ve seen the durability of response. There are multiple tumour types are responding. It’s very promising that we have a regimen without significant adverse events, very promising that we can give both drugs together. The durvalumab was initially given at 3mg and now at 10mg, which is the standard dose and the 0680 has moved up to 20mg dosage. This trial is now transitioned onto its phase II component which is a second line renal cell carcinoma component. It’s looking at randomising patients who have progressed off of a standard first line anti-VEGF therapy going on to either the one arm with the PD1 inhibitor, MEDI0680, versus the combination of MEDI0680 and durvalumab. It’s a very promising combination; the future of immuno-oncology will have to be in combination regimens and will have to be in combination regimens that are tolerable. I think this trial has met that endpoint in the phase I setting, a tolerable regimen, easy to give with minimal toxicity. We’ve seen a complete response and partial responses; we’ve been able to characterise the toxicity. I look forward to having future biomarker data from this cohort and from the renal cell carcinoma cohort. I urge patients looking for a novel approach to consider this trial, it’s open in multiple sites and is on

Was there any gene typing of their tumours ahead of time?

There is tissue evaluation but none of that has been presented yet. It’s a growing field of looking to see how we can increase response in PD-L1 negative tumours, or low expressers, but we’ve also sort of failed to mention that we’re not getting 100% responses in PD-L1 high expressers so a combination can hopefully get us there and possibly this combination. There’s a lot of preclinical evidence to show that this is an intelligent design so I look forward to future ESMO and future meetings where we can present some of the updated data from the phase II portion of the study.