Eric Jonasch, MD, on phase 1/2 trial of 177Lu-girentuximab combination in ccRCC

In this video, Eric Jonasch, MD, shares the rationale and design for the trial, “Phase 1b/2 study of combination ¹⁷⁷Lu-girentuximab plus cabozantinib and nivolumab in treatment naive patients with advanced clear cell RCC,” which was shared at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas. Jonasch is a professor of genitourinary medical oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas.

Video Transcript:

Currently in the frontline setting for advanced renal cell carcinoma, we're using what we call doublets, immune therapy and checkpoint blocking antibody therapy together with a targeted therapy or checkpoint blocking antibody therapy combinations. We're doing fairly well with those, but we could do better. What we are testing here is an agent called ¹⁷⁷Lu-girentuximab. Girentuximab is an antibody that interacts with carbonic anhydrase 9, which is expressed at very high levels in clear cell renal cell carcinoma cells. What we're looking for is we're looking to see whether or not adding lutetium, which is a beta emitter radioactive isotope, to girentuximab, together with cabozantinib, a TKI, plus nivolumab, results in higher complete response rate compared to historic data with the doublet and to see whether or not outcomes of individuals improves. It's a 100-patient study. It's what I would call tissue rich. It has a large number of biopsies and circulating analyzes as well. We really want to understand whether by using this beta emitter, together with the combination of cabazantinib and the nivolumab, we're getting better outcomes than we would expect with the doublet alone.

The primary end points are a complete response rate. We're expecting a higher complete response rate than the historic complete response rates. It's a 100-patient study, and it's not randomized. It will be multi center. Individuals will be enrolled. They have baseline imaging, which includes some novel imaging, looking at the activation of T cells. There's a particular PET modality that we're using there. Then patients will, for the beginning, get a dose of lutetium girentuximab, and then in the beginning of the second cycle, will then start getting cabazantinib and nivolumab. They get the ¹⁷⁷Lu-girentuximab every 12 weeks, up to 3 times. They'll be getting the cabazantib and nivolumab every 4 weeks in the usual way that this drug is given, with the cabazantinib given daily.

This transcript was AI generated and edited by human editors for clarity.