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GTB-5550: A Tri-specific NK Cell Engager Designed to Target B7-H3 - Nicholas Zorko

November 24, 2025

Zachary Klaassen is joined by Nicholas Zorko to discuss GTB-5550, a Tri-specific Killer Engager targeting B7-H3 in advanced prostate cancer. Dr. Zorko explains that B7-H3 represents a cell surface target beyond androgen receptor and PSMA, with multiple antibody drug conjugates under development across oncology. GTB-5550 comprises three components: CD16 for natural killer cell engagement, interleukin-15 as a flexible linker providing necessary cytokine signaling, and B7-H3 for tumor recognition. Dr. Zorko developed the first batch in 2019 during his postdoctoral work, with GMP production now complete and FDA submission planned for December 2025, targeting first patient dosing in April 2026. The trial will enroll hormone-resistant prostate cancer patients post-androgen receptor pathway inhibitor treatment, with expansion into bladder cancer leveraging B7-H3's pan-tumor expression.

Biographies:

Nicholas Zorko, MD, PhD, Assistant Professor, Department of Medicine, University of Minnesota, Minneapolis, MN

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA



Related Content:

A PSMA-Targeted Tri-Specific Killer Engager Enhances NK Cell Cytotoxicity Against Prostate Cancer - Beyond the Abstract

ESMO 2024: B7-H3 as Therapeutic Target for Prostate Cancer
Investigating the Role and Therapeutic Potential of B7-H3 in Prostate Cancer - Christina Guo

B7-H3 Targeting ADC in Castrate-Resistant Prostate Cancer Trial - Andrew Parsonson

Read the Full Video Transcript

Zachary Klaassen: Hello, welcome to UroToday. My name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined by Dr. Nick Zorko, who is professor of medicine, medical oncologist at the University of Minnesota. Today we're going to be talking about a new cell surface target, and specifically some new phase one trials that are going to be in progress here pretty quick. So Nick, thanks so much for joining us on UroToday.

Nicholas Zorko: Thanks for having me here at UroToday. It's always a pleasure being here, Zach.

Zachary Klaassen: It's great having conversations with you. So let's just level set for our listeners about these new targets. We've had androgen receptor forever, PSMA. Now tell us about this new class and we're really starting to see some new targets and new phase 1 trials undergoing.

Nicholas Zorko: So B7-H3 is a target that we've been very excited about at the University of Minnesota. It's a cell surface marker. We are not entirely sure its purpose, so we're really, in our purpose anyway, we're really just using it as a target. We're not looking at it as a pathway to block. There are other antibodies out there that are looking at this. Enoblituzumab was a great example in prostate cancer, and then there are also several other antibody drug conjugates under development that are in trials to target it. So we're not the only ones. It is an exciting target we think.

Zachary Klaassen: Awesome. And just tell us about the design of GTB-5550.

Nicholas Zorko: So GTB-5550 is a product that we developed at the University of Minnesota. It's called a Tri-specific Killer Engager or a TriKE, and there's three components to that. So the first part, we have to engage natural killer cell targeting CD16. Then we engage IL-15 or interleukin-15 as the flexible linker in the middle. And then we finally have a tumor associated antigen engager, in this case B7-H3.

Zachary Klaassen: So just for our listeners, from a TriKE to a bispecific antigen. So what's the benefit potentially of that added component?

Nicholas Zorko: So the difference between natural killer cells is that we found that they really need that cytokine signal to expand and activate. Unlike T-cell engagers that target CD3 or CD28, we need that third signal with NK cells.

Zachary Klaassen: Okay, perfect. And so development-wise, you guys developed it at University of Minnesota. Where are we at in the process? Maybe getting a phase one going for this?

Nicholas Zorko: Yeah, so this started when I was a postdoc in 2019. I made the first batch.

Zachary Klaassen: That's awesome.

Nicholas Zorko: So now we have a GMP product that's filed and we are waiting on some of the final in-use studies, and we're planning on submitting to the FDA at the end of December. So I'll be the IND and sponsor for that, which is really exciting to see a translational product go from the bench to the bedside and then potentially first patient dose in April.

Zachary Klaassen: That's awesome. So all those postdocs out there, six years later, just stick with it and then here we are getting an FDA submission to hopefully get a trial going.

Nicholas Zorko: Yeah.

Zachary Klaassen: That's awesome. Let's assume this is positive phase 1. We'll move into additional clinical data. How do you see this potentially fitting into the landscape with all these other targets?

Nicholas Zorko: That's a great question. One of the things that we really talk about NK cells at the University of Minnesota and others in the NK world, we talk about safety of NK cells. So there's much lower risk for cytokine release syndrome. There is no risk for neurologic toxicity as well. So the goal is potentially to move this to the outpatient stage for some of more remote patients who may not be near a center that's as experienced. So that's the goal if we see that safety there, but really late-stage prostate cancer to start with, hormone-resistant post at least one ARPI. I think this would ideally be something we could move forward as well, like we're seeing with the other products that are more the T-cell engagers.

Zachary Klaassen: That's awesome. And outpatient would be great. I mean, you live in Minnesota, a lot of rural patients that live in Georgia-

Nicholas Zorko: There really are.

Zachary Klaassen: I mean, that could be really beneficial.

Nicholas Zorko: So that's our goal working through the state of Minnesota, is to try to expand this as much as we can for those patients who can't drive six or seven hours to Minneapolis on a regular basis.

Zachary Klaassen: For sure. Congratulations on the persistence on getting this through in the next few months. Any take home messages, anything we haven't hit on that you want to talk about?

Nicholas Zorko: It's just an exciting time. We're hopeful with the NK cell engagers, we're moving that into bladder as well as part of that trial. So fitting with UroToday. So prostate and bladder and a number of other solid tumors. So I think B7-H3 is a great pan tumor target that I didn't mention, but...

Zachary Klaassen: Yeah.

Nicholas Zorko: Yeah.

Zachary Klaassen: That's awesome. I think if we look back even five years ago, pre-RLT, pre-VISION then this explosion that it seems like we're on the same cusp in this disease space as well.

Nicholas Zorko: I agree. I agree. It's going to be a really exciting time in the next couple of years.

Zachary Klaassen: Awesome. Nick, great conversation as always. Thanks for joining us.

Nicholas Zorko: Well, thanks for having me as always, too. Good talking with you.

Zachary Klaassen: You too.