Alicia Morgans: Hi. I'm so excited to be here with Dr. Rahul Aggarwal. We are talking about an oral abstract presentation that he gave at GU ASCO 2023. Thank you so much for being here with me today.

Rahul Aggarwal: It's my pleasure.

Alicia Morgans: Wonderful. So really exciting data in a really exciting session at GU ASCO. Can you tell me a little bit about your presentation?

Rahul Aggarwal: Sure, I'd be happy to. So this was part of the rapid oral abstract session at ASCO GU 2023, and it was a phase II study we did in patients with either de novo or treatment emergent small cell neuroendocrine prostate cancer, which we know is a very high risk group of patients with limited standard of care treatment options.

Alicia Morgans: Great. So tell me about the treatment.

Rahul Aggarwal: Sure. So this was a combination immunotherapy trial. So this was combining pembrolizumab, so an immune checkpoint inhibitor, with an investigational agent BXCL 701, which is a dipeptidyl peptidase inhibitor. It basically activates the innate immune system, induces inflammasome activation, cytokine chemokine production and immune cell infiltration within the tumor to achieve a better effect than we have seen historically with checkpoint inhibition alone.

Alicia Morgans: And I think immunotherapy and prostate cancer has been challenging as an approach. Certainly some patients with MSI high status, high TMB really can respond so well. But if there was a way to expand that population that might benefit, it would be really exciting, so what did you find?

Rahul Aggarwal: Yeah, absolutely. And in fact, we saw some durable responses. So our overall composite response rate was 25% in this study, including durable objective responses. And importantly, these were all patients that had low TMB and microsatellite stables. These are not patients that we would really predict would respond well to pembrolizumab alone, and over two thirds of our patients had had prior platinum-based chemotherapy. So this is a really heavily pre-treated patient population, really limited standard of care options, so to see durable responses in a subset of patients was really quite encouraging and it's led to our expansion to an next phase 2B study where we're now studying the combination of about 60 patients, so a larger study.

Alicia Morgans: Well, that's great. And certainly if you had two thirds of the patients exposed to platinum, this is a population of patients that's really pushing the boundaries of what commonly works for prostate cancer.

Rahul Aggarwal: That's exactly right. These patients really have either supportive care, maybe a second line chemotherapy that doesn't work well, very limited options, so I think these types of immunotherapy approaches are where the field is going in neuroendocrine prostate cancer and I think there's a number of exciting strategies. This one I think is distinguished by being fully outpatient based dosing. We use step dosing and split dosing, which really might mitigate some of the risk of cytokine release we see with other agents.

Alicia Morgans: So tell me a little bit about the toxicity profile.

Rahul Aggarwal: So in the first phase one, a safety lead-in study, we did see a fair amount of cytokine release which was manifested by hypertension, edema. When we implemented step dosing, so starting at two thirds of the dose in week one and then escalating to the full dose, as well as split dosing, we really saw a significant reduction in that type of toxicity. We still see grade one hypotension and edema, but it's very manageable with supportive care.

And then the immune related adverse events that we think about with pembrolizumab, we did see grade one, two events, but there was really only one grade three colitis event out of 34 patients that was reversible with supportive care. So we don't really think of it as necessarily leading to too high of a potentiation of those types of immune related adverse effects.

Alicia Morgans: Which is so important in these patients who can be very ill.

Rahul Aggarwal: They're very ill at entry, and you see that in the adverse event profile, a lot of non-related adverse events. These patients are sick, they do get admitted to the hospital pretty frequently.

Alicia Morgans: So were these adverse events or was the infusion, was it given in the hospital? Did these patients require a hospital stay to get this?

Rahul Aggarwal: No, it was fully outpatient, and actually, the BXCL 701 is an oral therapy that's given twice a day for two weeks on, one week off, which also helps to mitigate some of the side effects. And pembrolizumab, standard outpatient, Q3 week dosing.

Alicia Morgans: So important for these kinds of approaches, again, because some of our attempts have really required hospital stay.

Rahul Aggarwal: Very challenging.

Alicia Morgans: And supportive measures in that way.

Rahul Aggarwal: Yeah.

Alicia Morgans: Great. So if you had to tell us where you're going with this medication, you did mention the phase 2B. Tell us a little bit about that. It must be exciting.

Rahul Aggarwal: It's exciting. This is a space where you don't necessarily need to have a randomized 600 patient trial. I think there's a high unmet medical need, so where we're going is expanding a phase 2B study where we're going to aim to study a randomized study with 40 patients receiving the combination, 20 with BXCL 701 alone, because the contribution of components matters when we think about the registrational path. If we can see durable responses in a substantial proportion of patients, that could lead to potentially a regulatory path for approval for the combination.

Alicia Morgans: Great. So if you had to sum it all up, what would your message to listeners be?

Rahul Aggarwal: I think we're excited about this combination. We need more therapies. Hopefully, there'll be more immunotherapy options for these patients, but we're really excited about this combination and looking forward to seeing our results with the larger study.

Alicia Morgans: Well, I think we're all looking forward to that too, and congratulations to you, your fellow investigators, and certainly thank you to all of the patients who participated. We appreciate your time today.

Rahul Aggarwal: Thank you so much, Alicia.