Medicine Matters oncology

Regarding enfortumab's role, I absolutely see it being utilized in earlier stages of disease. There are two very pivotal studies that are currently ongoing-- cohort K of EV-103, and then EV-302. And let me walk you through two of these trials. What we observed early on is that there were some immunological properties to enfortumab, mostly based on anecdotal evidence by investigators like myself and others that saw some interesting clinical observations in patients who were treated with EV after immunotherapy.

And then that led to a small phase one-- EV-103-- that looked at EV plus pembro in the first line setting. So enfortumab vedotin plus PD-1 blockade first line metastatic urothelial cancer initially in patients who were cisplatin ineligible. And so there clearly already is a role for pembrolizumab monotherapy. And we saw a 73% objective response rate, 93% of patients achieving some measure of disease control and really promising durability to the combination. And to see a response rate as high as 70 plus percent something we don't see-- we've never seen before in advanced bladder cancer for that matter.

And so we wanted to test these hypotheses further-- cohort K of EV-103 So we added another arm to EV-103, which is now a very large phase one program. And that is enrolling 150 patients and randomizing first line cisplatin ineligible patients to either EV monotherapy or EV plus pembro. And this randomization is really important because we need to understand the contribution of components here between pembro and EV. And so that study is ongoing.

And then the other, which is EV-302, is a very large multinational phase three trial randomizing patients to either EV plus pembro, which is the kind of experimental arm, versus a one to one ratio platinum based chemotherapy-- either cis plus gemcitabine or carboplatin plus gemcitabine. And so this is all-comer patients, cisplatin eligible and ineligible with the fundamental question, is EV plus pembro potentially a new standard of care in all platinum eligible patients, whether cisplatin or carboplatin?

The other area where I see enfortumab being incorporated into the treatment paradigm is in early stage disease. So now there are currently ongoing studies of the EV plus pembro in the neoadjuvant setting prior to cystectomy and muscle invasive bladder cancer, which is involving basically perioperative therapy before and after. We know that for cisplatin ineligible patients, radical cystectomy alone is considered a standard of care. And we know that cisplatin previously improved survival. In the muscle invasive disease setting, it improves cure rates.

But for patients that are not eligible for this cisplatinum, they get cystectomy alone. And so now, we're testing this part of it in an ongoing phase three of cystectomy alone versus pembro followed by cystectomy and adjuvant pembro versus EV plus pembro followed by cystectomy followed by adjuvant EV pembro, and asking the question essentially, does this combination improve our cure rates for cisplatin ineligible patients of muscle invasive bladder cancer that are undergoing cystectomy?