GU Cancers 2021 | Exciting ongoing trials in urothelial cancer

I think it’s important to highlight multiple trials in progress in the meeting. And we’re very excited about these two particular trials. I will start with the bintrafusp alfa. This is an interesting molecule inhibiting PD-L1 and TGF-beta at the same time. This is a trial a single-arm Phase II trial in platinum-refractory advanced urothelial cancer. So, second-line setting in patients who had progression on platinum-based chemotherapy, but have not received immunotherapy yet, immunotherapy-naïve patients. And we tried to look at the overall response rate with this molecule, the anti PD-L1 and the TGF-beta molecule the bintrafusp alfa, and we have an interim futility analysis. I think the whole study is about 40 patients with a futility analysis built in. It’s a proof-of-principle study to see whether we get a very good signal of efficacy in those patients and the notion, the foundation behind the design of this study is the very interesting molecular data, biomarker data, from our group and others, Dr Maria De Santis, Dr Galsky, ourselves and others, that suggest that TGF-beta in the tumor microenvironment may be a mechanism of resistance to anti PD-L1 therapy.

So because of that, we thought that if we inhibit both PD-L1 and TGF-beta, we can potentially reverse inherent resistance to checkpoint inhibitors. So, we’re very excited about this design and concurrent inhibition of TGF-beta as the mechanism of resistant to checkpoint inhibitor with PD-L1 inhibition, and we’ll have to see what the trial shows.

The second trial that you mentioned, TROPiCS-04, a Phase III trial, we’re very excited about it. So just to provide context for the audience, this is a Phase III trial evaluating the antibody drug conjugate sacituzumab govitecan. The previous name was IMMU132. This is an antibody drug conjugate against Trop-2, conjugated or linked with a toxin payload, the SN-38, which is sacituzumab govitecan, a TOP1 inhibitor.

So, this agent in previous Phase II trial called Trophy-U-01 study, in the cohort one presented by Dr Loriot and ourselves, our group at ESMO 2020. So that the overall response rate in heavily pre-treated patients was 27%, treated with single agent sacituzumab govitecan in patients with prior chemotherapy, immunotherapy and maybe other therapies. The range of prior therapies in the Trophy-U-01 cohort one was I think between three and nine prior lines of therapy. So, heavily pre-treated population overall response rate 27%. And that actually prompted this Phase III trial comparing sacituzumab govitecan to physician’s choice chemotherapy, for example, single agent taxine in US or vinflunine in Europe and the primary points overall survival.

The design of this TROPiCS-04 trial is very similar to the EV-301 trial that was just presented by Dr Powles at the ASCO GU 2021 and showed an overall survival benefit with enfortumab vedotin, and so I think it is very important to evaluate further this impressive signal with sacituzumab govitecan from the Phase II trial. And I will see if we can hopefully accrue quickly and appropriately in this Phase III confirmatory trial called TROPiCS-04. We’re very excited about it.