Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Ongoing trials evaluating immunotherapies in combination with targeted therapies for metastatic RCC
5:10 minutes.
TRANSCRIPTION:
DR LOVE: What are some of the new strategies incorporating checkpoint inhibitors that you’re most excited about in addition to these combinations? What about targeted therapy and immunotherapy, for example? DR RINI: Yes. So that’s the latest combination wave, the immuno/immuno with ipi. Nivo was first. There’s a large Phase II and a separate Phase III with atezolizumab, a PD-L1 inhibitor, recently approved in bladder, and bevacizumab in combination. And also the atezolizumab as monotherapy in a sunitinib control arm. So that randomized Phase II data, it’s been accrued and probably will be reported as a first signal of really comparative efficacy, although again, a randomized Phase II. A lot of patients were treated on those 2 separate trials. And then most recently has been the checkpoint inhibitors plus TKIs. So perhaps most exciting was reported at ESMO by Mike Atkins, is pembrolizumab plus axitinib. And so axitinib has also emerged as the darling partner of this I-O agents, I think in part based on its tolerability — it seems to be very combinable. Whereas some of the other TKIs, pazopanib and sunitinib, notably, haven't quite been as tolerated. So the axitinib/pembrolizumab or axi/pembro, as we often shorten it to, was reported at ESMO in a cohort of about 50 patients, 52, something like that, and reported a response rate of about 70% — which is exceedingly notable — with almost all patients showing tumor shrinkage. So early days. We don’t have mature follow-up for PFS, et cetera. But at least at first blush, that level of activity we’ve not seen before. DR LOVE: What do we know about the efficacy of atezo alone in RCC? DR RINI: I don’t think we know anything. There was just a Phase I with a handful of RCC patients, a IB, I believe. And I can picture the spider plots, so there’s definitely some activity, but I think it’s relatively minimal. And it wasn’t really developed as a single agent for RCC. DR LOVE: But the trial that you were talking about, so that’s atezo and what was it? DR RINI: Atezo and bevacizumab. That combination. DR LOVE: Oh, so really, if atezo’s going to be used in renal, it would have to kind of be that way then. DR RINI: The registration trial is that combination compared to sunitinib. So if it’s going to get approved, it’s that combo that would likely get approved. In the randomized Phase II, there was an atezo monotherapy arm. We will have a little bit of data once that trial emerges for monotherapy. DR LOVE: Any thoughts about anti-angiogenics, including — I’ve heard about bev on and off, being brought up in some way having an immunologic activity. The theoretical reason why, maybe there would be synergy between anti-angiogenic and a checkpoint inhibitor. DR RINI: Yes. I mean, there has been a lot of work over the years, some from our folks at Cleveland Clinic and many other places looking at the potential immunomodulatory role of the VEGF agents. Sunitinib has a fair amount of data. Bev, as you say. And there does seem to be something there. There seems to be some downregulation of immunosuppressive cells, like regulatory T-cells and myeloid-derived suppressor cells. Some promotion of cytotoxic T-cell cytokine production. And so that’s mostly peripheral blood data. It’s not necessarily tumor biopsies. So there’s some data to support it. At the end of the day, a lot of these combinations are purely empiric clinical combinations. You have active drug A and active drug B and their different mechanisms, and we put them together. And so far it seems that there’s activity to those combos. DR LOVE: So we’ve talked a little bit about the nivo data, nivo combination, atezo data. What about pembro? DR RINI: So pembro has combination data with axitinib, that I mentioned, and that’s moved on to a Phase III that’s just starting — again, compared with sunitinib. These are all really compared to sunitinib as the control. DR LOVE: What about pembro alone as second-line therapy? DR RINI: So there is no data of pembro as second-line therapy. There’s a separate trial from the Phase III that’s looking at pembro as monotherapy in front line and also in nonclear cell. So kind of a separate question related to, obviously, the Phase III development strategy but separate. So we don’t really have lots of pembro mono data in kidney cancer. In fact, I’m not sure I can think of any off hand — I don’t know if they’re in Phase I data or things like that. But no Phase II and beyond data yet. DR LOVE: What about durvalumab and tremelimumab? DR RINI: So durvalumab and treme, they’ve not been given to kidney cancer patients to my knowledge. Certainly, again, maybe a handful in the Phase I. We’re actually going to be doing a neoadjuvant trial with those drugs, mostly to look at tissue and blood-based endpoints and immunologic endpoints. So we’ll get some data there. But again, that’s in a locally advanced setting, not a metastatic setting. So I don’t know that there’s a plan to develop them for metastatic disease. I think they’re pursuing other indications. |