GU Cancers 2021 | TROPiCS-04: sacituzumab govetican in mUC

For patients with metastatic or advanced urothelial carcinoma beyond platinum-based chemotherapy, immune checkpoint inhibitors, we now know enfortumab vedotin, as well as the subset that happened to have a pathogenic mutation or fusion of the FGFR-2 or 3 pathway, that remains an unmet need. So there are patients that still have a performance status that warrants additional therapy, but there’s not a lot of options. We know that sacituzumab govitecan is an antibody-drug conjugate that’s approved currently in the United States for triple-negative breast cancer, has some interesting and promising data for the metastatic urothelial carcinoma population.

With initial data on 45 patients presented a couple of years ago at the Genitourinary Cancer Symposium with promising data and then a prospective Phase II trial of 113 patients in the TROPHY-U-01 study presented at ESMO 2019 and 2020 with response rates of 27% in a heavily pretreated patient population. That drug now with breakthrough definition could in theory receive accelerated approval like enfortumab vedotin, have currently, but we really expect that to, EV, to have full approval soon.

So that has led to what is a potential confirmatory trial, which is TROPiCS-04. So that’s a Phase III randomized trial of men that have had at least platinum-based chemotherapy, as well as an immune checkpoint inhibitor. There is no limit to prior therapy, as long as at least one of the control drugs is available. Most explicitly, I don’t think that everyone captures, that means that patients could have received enfortumab vedotin, although that is not required, patients could have received an FGFR-targeted drugs such as erdafitinib, although that is not required. So, any one of those or more is allowed prior to enrollment in the study. So as long as the patients maintain a performance status of 01, they can enroll to receive either a randomized to sacituzumab govitecan at the same dosing schedule as before, day one to eight of a 21-day regimen, versus in the United States or locations that don’t have vinflunine approved will be either docetaxel or paclitaxel, and in countries where vinflunine it was approved, they could get that drug as well.

That is a study that has been activated with the endpoint of overall survival. So, hopefully for our patients, we may have availability of that drug. I guess taxine we have that available off-label today, but hopefully there is accelerated approval of that drug. But in the meantime, a Phase III randomized trial has now been initiated, and we hope that that leads to worldwide approval for this promising drug down the line, because our patients certainly could use additional therapy when available.