Lung Cancer Update, Issue 3, 2016 (Video Program) - Video 27Activity and tolerability of the antimesothelin antibody-drug conjugate anetumab ravtansine for mesothelioma
4:37 minutes.
TRANSCRIPTION:
DR BLUMENSCHEIN: So this is an interesting compound. And as you mentioned, it’s an ADC, so it targets mesothelin, which is, obviously, very highly expressed, on the order of 100% in mesothelioma and minimally so in normal tissue. And you look for that in an ADC. You don’t want to have off-target cytotoxicity. And what the ADC does is, it has a payload and the compound mates with the receptor and is internalized into the cancer cell and the payload is delivered. And this was a Phase I trial, and we saw activity in both peritoneal and pleural mesothelioma, with responses in patients who were heavily pretreated. And in patients who had 1 prior line of treatment, the response rates were over 40%. So was a very robust response in this large Phase I. And this has now led to an ongoing Phase II effort, which is currently accruing patients, and plans to move into the front-line setting and then into other tumor types, which have overexpression of mesothelin. DR LOVE: Have you had patients, yourself, receive this agent who had what you thought were clinical useful responses? DR BLUMENSCHEIN: Yes. So I actually have a patient who has peritoneal mesothelioma who has been on this therapy for greater than a year and tolerating treatment well and having good quality of life. So yes, I’ve seen patients who have benefited from this. DR LOVE: Now this patient, though, had objective response? DR BLUMENSCHEIN: Yes. Had objective response. DR LOVE: Hmm. Interesting. And what kinds of toxicity issues? With B-vedotin we saw peripheral neuropathy, T-DM1, a couple of other things. LFTs, platelets. What do you see, if anything, with this agent? DR BLUMENSCHEIN: So you see some neuropathy. And we noted in patients who had multiple lines of therapy, including several lines of taxanes, there was an increase in peripheral neuropathy. But the real rate limiter on this was actually corneal epithelialization. Essentially, you epithelialize your cornea. So we had to work around that. And what it essentially involved was early identification, close monitoring with an ophthalmologist and dose adjustments and/or dose holds. And this is something that’s self-contained and resolves. DR LOVE: Yes, it’s interesting that — I can’t remember, like — on your general oncology, you hear things in different places I can’t remember. But I remember hearing about an antibody-drug conjugate, I think it was in ovarian cancer, that also caused ophthalmologic. It sounds kind of like what you just described. DR BLUMENSCHEIN: Yes. Actually, it’s been seen in a number of drugs in this class. And it’s likely due to the payload utilized. So it’s a class effect. And various management strategies are being developed around that. DR LOVE: So you also at ASCO had the Trial in Progress poster about the Phase II study that you were describing that came out of this. Really, it sounds kind of exciting, actually, particularly for mesothelioma. What about the Phase II trial? How long do you think it’s going to take to see some results from that? DR BLUMENSCHEIN: The study is actually accruing quite well. And this is a randomized study of the ADC versus vinorelbine. And the study’s actually accruing ahead of schedule. So it’s open currently. It’s exceeding its time points in terms of patient accrual. There’s a lot of enthusiasm for it. And so I think we should have results from this within, I would think, the next year to year and a half. DR LOVE: What’s, from your point of view, what’s the primary endpoint? And, I don’t know, the thinking in terms of the potential of bringing this into practice? DR BLUMENSCHEIN: I think for the study we’re looking at, things such as response, progression-free survival, I think the scope of this is, if we take a step back is that mesothelioma, currently there’s 1 approved approach and that’s utilization of pemetrexed with a platinum agent in the front-line setting. There is no approved second-line option for patients. Oftentimes we’ll use other cytotoxics, such as gemcitabine. But there really is no second-line option. And as we saw from this past ASCO, there’ve been some clinical trials exploring the utilization of immunotherapy. For example, there was a study with CTLA-4 versus placebo, which is a randomized Phase III trial, which was actually a negative study. But right now it’s an underserved population. It’s a population at need. And so I think this will provide, if it’s a positive outcome, this will provide a new option for patients. |