Alicia Morgans: Hi, my name is Alicia Morgans and I'm a Geo-Medical Oncologist at Dana-Farber Cancer Institute. I'm so excited to have here with me today, a good friend and colleague, Dr. Neeraj Agarwal:, who's a professor in medicine and the director of the Geo-oncology program at the Huntsman Cancer Institute. Thank you so much for being here with me today.

Neeraj Agarwal: Thank you for having me. Always a pleasure.

Alicia Morgans: Always a pleasure for me too and I'm always excited to talk with you about the exciting things that you're working on. In this case, TALAPRO-3

Neeraj Agarwal: Yes. So TALAPRO-3 trial is trial for patients with metastatic castrate-sensitive prostate cancer. So we have heard more about TALAPRO-2 trial, which is in metastatic castrate-resistant prostate cancer setting, but this is in sensitive setting. So in this trial, patients are being randomized to androgen deprivation therapy, plus enzalutamide, plus [inaudible 00:00:53], which is a PARP inhibitor, as we know. The primary endpoint is radiographic progression-free survival, and a very important eligibility criteria is that patients have to have tumors harboring DNA repair gene mutations. So they have to have homologous-three combination repair defect. This is not for all patients. So this is for selected patient population.

There are multiple other secondary endpoints, including overall survival, quality of life, which who can tell better than you is probably one of the most important endpoints in today's times when we are treating patients with these upfront, more intensive therapies. And trial is a global trial, is a multinational trial, is open in more than 20 countries. So we are really hoping that a combination of androgen deprivation therapy with enzalutamide with [inaudible 00:01:57] will ultimately, be proven to be superior to the combination of [inaudible 00:02:04] plus enzalutamide for patients with metastatic castrations sensitive prostate cancer, harboring these DNA repair defects.

Alicia Morgans: And what an exciting trial and opportunity for the metastatic hormone sensitive patient population at GUASCO 2022. We certainly heard that the combination of an AR-targeted approach plus a PARP inhibitor seems to be really beneficial in a more advanced castration resistance setting. It's exciting to think, and to know that you and the team are looking at this in a hormone sensitive population.

Neeraj Agarwal: Yes, absolutely. We know based on the preclinical data that there is interdependency between the AR and the PARP pathway. PARP has been shown to support AR function, if you will. And when you use PARP inhibitors, the prostate cancer cell is expected to be more sensitive to AR targeting and vice versa. So AR targeting of the cell is supposed to induce brokenness inside the cell. So all those laboratory-based rationale are fine, but we are really looking forward to see real efficacy in our patients, which will it so compelling down the line.

Alicia Morgans: I agree. And I love that you are really building on a control backbone of the combination AR-targeted agent in enzalutamide. You're having such a very effective control arm. And then you're adding the [inaudible 00:03:36], which of course is a high bar, but is the right bar for our patients at this point?

Neeraj Agarwal: Absolutely. We do not think we can use substandard controls anymore in our patients. It is unjustifiable. So I'm really hoping that we'll see positive signal and we'll get one more options available for our patients.

Alicia Morgans: Absolutely. So for those who are interested, we'll make sure to put the clinicaltrials.gov link up so we can ensure that people have access and certainly clinicaltrials.gov is a place where people can go to identify if there's a center nearby. And it sounds like this trial is open pretty broadly and really is hoping to continue to enroll patients.

Neeraj Agarwal: Absolutely. This is very important and I know UroToday has done such a wonderful job of making our patients aware of all these opportunities and trials. So please keep it on.

Alicia Morgans: Absolutely. Well, thank you so much for your time and your expertise, and I hope to talk to you in a few years so we can discuss the results of what I believe is going to be of very positive trial.

Neeraj Agarwal: Yes, we look forward to it. Thank you.