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IZABRIGHT Trial Tests Dual HER1/HER3 ADC Against Platinum Chemotherapy in Urothelial Cancer - Thomas Powles

March 9, 2026

Thomas Powles presents IZABRIGHT, a global randomized Phase III trial testing izalontamab brengitecan, a dual HER1/HER3 antibody-drug conjugate with topoisomerase payload, versus platinum-based chemotherapy in second- or third-line urothelial cancer. Chinese data demonstrated response rates exceeding 40%. The majority of urothelial cancer patients express both HER1 and HER3. A randomized Phase II component determines optimal dosing before transitioning to Phase III. 

Biographies:

Thomas Powles, MBBS, MRCP, MD, Professor of Genitourinary Oncology, Director, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, London, United Kingdom

Tian Zhang, MD, MHS, Associate Professor, Department of Internal Medicine, Associate Director of Clinical Research, Simmons Comprehensive Cancer Center, Director of Clinical Research, Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX

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Read the Full Video Transcript

Tian Zhang: Hi. Thanks for joining me on UroToday. My name is Tian Zhang. I'm a GU medical oncologist at UT Southwestern in Dallas, Texas. I'm joined today by my very dear friend and colleague, Dr. Tom Powles. Tell us a little bit about your trial and progress, IZABRIGHT.

Thomas Powles: So this is a big global randomized phase three international study. Lots and lots of different people and lots of sites were involved. There are some new ADCs being developed inevitably. We now have EV pembrolizumab as frontline disease. What do we do second and third line? And platinum-based chemotherapy is a classic second-line treatment, but we don't love it. I don't love it. I hope we can do better, and the question is are there ADCs, the compete platinum-based chemotherapy? There's a drug called Iza-Bren (izalontamab brengitecan, BL-B01D1). It is a dual HER1, HER3 ADC with a topoisomerase payload. We have tested it from Chinese data. We've tested it and we've shown really quite good activity response rates above 40%. It's got positive randomized ... There's a positive randomized trial I think in breast cancer announced just recently, and so it's got a lot of momentum behind it. It does look an active drug, and we're just doing a randomized study. It literally has a randomized phase two component, just a test to make sure we get the right dose. We're going to take the correct dose out of that randomized phase two into a big global randomized phase three. We're looking for a great result.

We want to beat platinum chemotherapy. We believe we can do it. The toxicities associated with the topoisomerase inhibitor, so you can imagine neutropenia, fatigue, diarrhea, potentially hair loss, classic adverse events. HER1 and HER3 quite heavily are expressed in urothelial cancer, actually. The vast majority of the patients express both. It's not widely as targeted as before, but we know we've targeted HER2 successfully. Why not HER1 and HER3? Take part in the trial. I think it's going to be successful.

Tian Zhang: Yeah. If somebody wanted to send their patient, where is it open?

Thomas Powles: It's opening globally.

Tian Zhang: Yeah.

Thomas Powles: Yeah. So it's on clinicaltrials.gov. I think the first patient was enrolled in Australia. We've enrolled a patient at our hospital. There are sites opening up all over the world as we speak. It's going to be cool.

Tian Zhang: Exciting times, Tom. Thank you so much.

Thomas Powles: Thank you.