Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU medical oncologist and Associate Professor of Medicine at Northwestern University. I'm so excited to have here with me today a friend and colleague, Dr. Karim Fizazi, who is a Professor of Oncology at Gustave Roussy in Paris, France, where he is also a GU medical oncologist. Thank you so much for being here with me today, Karim.

Karim Fizazi: Always a pleasure, Alicia. Thank you for having me here.

Alicia Morgans: Wonderful. So, I wanted to speak with you today about a presentation at ASCO GU this year. Of course, it's a virtual event, but you were able to participate in the CheckMate 9KD trial, and I'm wondering if you could tell us a little bit about that study?

Karim Fizazi: Sure. So this is a combo Phase II trial looking at docetaxel in association with nivolumab for men with metastatic castration-resistant prostate cancer, who basically are candidates for first-line chemotherapy for mCRPC. Part of the population had received a prior next-generation hormonal agent, either abiraterone or enzalutamide, and another part had not received those agents previously. So it's a quite large Phase II program combining nivolumab with various agents. Here, docetaxel obviously, but there are also two other arms. The trial is now maturing. This is a final analysis that we're reporting with nivolumab and docetaxel. And again, it's a quite large program. For example, for Vestrata, we included 84 patients, I believe. So, quite a large group, and the data looked good overall in terms of efficacy. The two primary endpoints were PSR response rate and overall response rate in men that have a RECIST assessable disease.

And actually what we saw was approximately the 60% response rate by PSA in men who have not seen abiraterone or enzalutamide with a combo and approximately 40% in those men who had already exhausted abiraterone or enzalutamide. I guess, not bad. And if compared probably a little better as compared to what you might expect with docetaxel, single agent. Of course, we don't have a control arm, so it's hard to make sure what exactly is the contribution from nivolumab, but I guess it compares favorably and at the same applied for the co-primary endpoint of RECIST response, what we saw was approximately a 40% response rate. And actually, this was regardless of whether the patient had received next-generation hormonal agents or not. So it was quite the same degree of efficacy by RECIST. So not bad I guess, regarding the response rate.

Alicia Morgans: Yeah, I think it's, it's really interesting. And certainly just to understand how this was delivered, this was nivolumab given with every docetaxel cycle during the docetaxel period, and when patients had completed their docetaxel, then they would get monthly nivolumab sort of in perpetuity until progression. Is that true?

Karim Fizazi: Correct. Treatment was given three times weekly together with docetaxel and then as a maintenance nivolumab treatment for patients not progressing before then. Correct, absolutely.

Alicia Morgans: Wonderful. So how do patients seem to tolerate it? And if you can give us a sense, what was the duration of response for those patients who did seem to respond?

Karim Fizazi: Right. So the duration of response was also quite good again, it's hard to know what nivolumab adds on top of docetaxel. But what we saw was approximately nine months as a median and actually even longer for patients who had not received enzalutamide or abiraterone so, as we all know, it's more in typically six, seven, eight months with docetaxel as a single agent. So I guess it compares well now really without a control arm, it's really hard to know the incremental benefit of the nivolumab added on top of docetaxel.

Now regarding the safety, generally speaking, what we so was what we know from both agents. So chemotherapy toxicity and nivolumab toxicity, nothing big really popped up. Perhaps I should mention that one man died of pneumonitis, and two other patients developed pneumonia and died of pneumonia. Again, small numbers, but I guess this is something we should be cautious about. Phase III is currently using this combination and comparing nivo plus docetaxel versus docetaxel alone. And of course, the IDMC is paying a lot of attention to the safety profile of the combo, which I think is very reasonable, but I guess so far so good. And again, the general profile of a combo was what you would have expected probably with both agents' user levels.

Alicia Morgans: I agree, but I think it's important and good, as you mentioned, that we do have a Phase III where we can actually look at this in terms of a comparison between all patients getting that docetaxel and then half getting nivolumab so we can really understand is there a safety signal related to the nivolumab that we need to worry about? Is this something that's only to the docetaxel, or is this just a fluke in a small Phase II that we happen to identify and really those larger phase threes will help us to sort that out, which is important and it's good. So if you had to summarize this work and give a message to those who are listening and really keen to learn at GU ASCO 2021, what would your message be?

Karim Fizazi: Well, right. I guess I would say that we see clear efficacy with docetaxel nivolumab. Safety is mostly as expected. Duration of efficacy is promising. Now without a control arm, it's very hard to say whether this is truly incremental as compared to docetaxel alone. And the Phase III, which is currently occurring, patients will tell. And on top of that, we're waiting for biomarker data in this Phase II. And I think this will be very important to look at.

Alicia Morgans: I agree, and I think it'll be exciting and interesting to look too at the other combinations that are included in this CheckMate study, where we are looking at nivolumab with other agents as well. So more to come and hopefully some biomarker data to help us understand how we can direct patients to the right combination or single-agent that may be best for them. So thank you so much for sharing your study and for your expertise, we always appreciate talking with you on UroToday.

Karim Fizazi: Thank you very much, Alicia. So have a great day.