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Alicia Morgans: Hi. I'm excited to have here with me today Dr. Brad McGregor who's an Instructor in Medicine at Harvard Medical School and a GU Medical Oncologist at the Dana Farber. Thank you so much for being here.

Brad McGregor: Thank you for having me.

Alicia Morgans: Of course. I am really excited about the work you're doing looking at rare GU histologies and trying to find treatment options for some populations that aren't so common and aren't always included in our clinical trials. Can you tell me about how that's an important thing to do and why we should even think that's something to consider?

Brad McGregor: Well, absolutely. I think when we think about clinical trials, unfortunately, most of the clinical trials are developed and designed for the most common subtypes. So when we think about bladder cancer or prostate cancer, when you have those atypical variant histologies. So bladder cancer maybe, adenocarcinoma, small cell, those patients are excluded. Same for prostate cancer. Or they're just rare tumors in general, like adrenal cortical carcinoma, penile carcinoma. So you have patients that come into Boston, "Say, hey I want to enroll in a clinical trial. I want something different." And we really didn't have anything to offer them.

So, given the tumor agnostic approach of immunotherapy, sort of activity across a wide variety of tumors. We really were looking to harness the activity and explore that in sort of these forgotten patients, so those patients with those rare histologies. That was the basis for the trial we've actually called the Rare GU Trial.

Alicia Morgans: Okay. Great. So what is the protocol, what does it look like for the patient who wants to enroll in that trial, and who are those patients?

Brad McGregor: So, the trial initial’s design was sort of three large cohorts. So those with bladder cancer of varying histologies, those with adrenal cortical carcinoma, and sort of the other groups. The other group included small cell of the prostate or other varying histologies of the prostate, as well as penile carcinoma and also treatment refractory germ cell tumors. So those patients who are progressed after platinum and high-dose chemotherapy. Those you have these three cohorts that we were looking at. And all the patients received nivolumab and ipilimumab at the sort of low dose ipi, high dose nivo. Some of what was used in the CheckMate 214 studies. There were three cohorts of 19 patients each.

Alicia Morgans: Okay. Wow. So how long did it take you to accrue?

Brad McGregor: We opened this through Dana-Farber, but it was open actually across the U.S. and MD Anderson and UCSD and more recently Ohio State and Emory. And we opened it just in the January of 2018 and within the past year, we've actually pretty much completed accrual. There's a few spots remaining in the adrenal cortical carcinoma and the other cohort, but we hope to complete accrual soon. And the bladder cohort has actually already completed accrual.

Alicia Morgans: Great. So when can we expect to see some data from the bladder cohort if it's completed accrual?

Brad McGregor: We're excited to say we submitted an abstract to ASCO and it's actually been accepted for a poster discussion at ASCO. So we'll have much more to talk about in just a couple of months.

Alicia Morgans: Okay. Fantastic. I know that you can't give us data, of course. In general, for these patients, these are metastatic patients who had either rare bladder histologies or this other group ... or these just generally rare GU tumor types. How did they tolerate this combination of ipi/nivo. And the reason I ask this question is because when we looked at ipi/nivo in prostate cancer populations, we just heard discussion of this at GU ASCO it was really hard to get all the cycles of therapy into these patients and certainly we know these treatments only work if they get into the patients and, of course, are effective. But if you can't even get them into the patient safely then it's going to be a problem. And I don't know if that's too big of a question to even ask, but generally, how did you feel it was tolerated?

Brad McGregor: I think overall what our experience on the trial was comparable to what we've had using this regimen in renal cell carcinoma. So certainly there are toxicities that have to be managed, but with appropriate use of steroids, this was a manageable regimen for the patients. And we did see some good responses in patients. Certainly is a very intriguing option.

Alicia Morgans: The other reason I think this is so exciting is that I think that people are already trying to do these treatments, the IO type approach, not necessarily the combinatorial approach, but the IO at least type approach in patients who have refractory small cell or who have these other histologies. It's most important that we actually have the data from clinical trials to support whether that's going to be effective or not. And this is not necessarily a practice defining trial but one that will give us a signal if there is one, I think, so that we can make those larger trials and really accrue even more broadly in those trials. What are your thoughts?

Brad McGregor: I agree. I think before this trial was open when you have a patient that comes in with adrenal cortical carcinoma we would pursue something like pembrolizumab or avelumab based on the JAVELIN data and the Phase 1 data. So that was something that was already being offered to patients. So I think it's a great opportunity to pursue these on a clinical trial where we can really gather information, not just for efficacy but also for toxicity as you pointed out. Just because this regimen can be tolerated in one cancer, there seems to be some variability in tolerability based on the malignancy itself. So it really gave us the opportunity to explore, not just efficacy, but tolerability across a wide variety of patients and tumor types.

Alicia Morgans: Wonderful. So what are the next steps? Of course, accruing these other two cohorts, but next steps.

Brad McGregor: So, I would say that given some of the preliminary data we've seen with the bladder cohort, we've actually been able to talk with the sponsors and open up an additional cohort. So we're going to open up a cohort in the next month really looking at those patients with neuroendocrine variants of any GU malignancy be it prostate or bladder potentially, or really any GU neuroendocrine variation. So that's going to be another 19 patients, and that cohort is going to be opening very soon. We really look forward to exploring this combination of those patients, specifically in treatment emergent, small cell, where options are often limited, especially after platinum therapy, and see how this combination is able to help those patients.

Alicia Morgans: Wonderful. And so for patients who are interested but don't necessarily live here in Boston and these rare histologies can hit anywhere, can you just remind everybody what are some of the other sites? And even if they don't live near one of those sites they can probably go on clinicaltrials.gov and potentially seek something out. But what are the other sites?

Brad McGregor: It's going to be opening here as well as down at Emory, MD Anderson, UC San Diego, as well as Ohio State. So across the country.

Alicia Morgans: Across the country. So really commendable that you are identifying a group of patients who are not included in most of our clinical trials, to give them the opportunity to have these therapies but also to gather information so that the rest of us know - are the things that we're doing off-label actually going to benefit our patients? So a fantastic way for you to use your strategies here and give opportunities to patients and educate the rest of us. So thank you so much for your time.

Brad McGregor: Thank you.