New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
PD-L1 expression and response to anti-PD-1/anti-PD-L1 antibodies
2:32 minutes.
TRANSCRIPTION:
DR SPIGEL: The 2 kind of leading PD-L1 agents right now are the 4736 compound and then, of course, MPDL3280A compound. We first heard about that a couple of years ago in a Phase I setting, patients with refractory tumors. So what was published recently in Nature was kind of a broad experience of that development, bladder cancer, the Phase I experience. And it’s just trying to see where this drug is active. The Nature paper, Roy Herbst was first author. It basically described that Phase I group, so it was a mix of a lot of different kinds of patients. When we look at the lung cancer patients who went on that study, heavily pretreated patients, when you combined them in an unselected way, the response rate was just over 20%. So, that kind of fits with everything we’ve been seeing across the board. What’s interesting in the MPDL development is so far they’re seeing strong signals in patients who have so-called PD-L1-positive tumors, whether that’s measured as 2+ and 3+ together or 3+, the response rates, numbers are tiny, can get upwards of 80-plus percent in that group of patients. So we’re waiting to see the results of some pivotal studies. The MPDL pivotal trials are pretty simple. The most — the one that’s going to be the most important, I think, is the OAK study. This is a randomized Phase III study that is identical to the nivolumab trial. It’s MPDL versus docetaxel in unselected patients. That includes adeno and squamous patients, whereas nivolumab was split. And then they have an interesting trial that is called the BIRCH study. So BIRCH is an interesting trial. You have to be PD-L1 to get onto it. You can be first line, you can be second line or you can be third and beyond and actually have brain metastases. So that’s 3 different cohorts that are being studied, all PD-L1-positive. That trial is going to be the one that they file with, those data. DR CARBONE: A quick comment that the MPDL agents, PD-L1 assay looks at immune — PD-L1 expression on immune cells and not on tumor cells. DR SPIGEL: Yes. We also — actually, it’s both. In the Nature paper, that’s correct that they looked at both. And you can see responses in PD-L1-positive tumor cells and PD-L1-positive so-called tumor infiltrating lymphocytes. It turns out that the latter group is perhaps a better predictor, at least in that paper, for a response to therapy. |