Commentary

Video

Circulating KIM-1 shows value as a biomarker in renal cell carcinoma

“The first one [is] we confirmed the prognostic value of KIM-1. Overall, in INmotion010, patients with high KIM-1 clearly had a higher risk of recurrence,” says Laurence Albiges, MD, PhD.

In this video, Laurence Albiges, MD, PhD, shares the background and notable findings from the study, “Circulating kidney injury molecule-1 (KIM-1) biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant (adj) atezolizumab (atezo) vs placebo (pbo) in patients (pts) with renal cell carcinoma (RCC) at increased risk of recurrence after resection,” which was presented at the 2024 ASCO Annual Meeting in Chicago, Illinois. Albiges is a medical oncologist focused on genitourinary malignancies and head of the department of oncology at Gustave Roussy Institute in Paris, France.

Video Transcript:

So, there have been different adjuvant studies [that] clearly depict that there may be some patients of the population who will derive benefit from adjuvant immune checkpoint inhibitors, while others may not. So, there is a need of a biomarker. What we are presenting is the first circulating biomarker analysis conducted in adjuvant trials with immune checkpoint inhibitors. It is a 2-step analysis, which looks specifically at circulating protein. The first part was about discovery. We screened over 3000 protein circulating biomarkers to assess the ones that were more likely to be highly expressed at the time of disease recurrence vs baseline post-nephrectomy. One circulating biomarker [stood] out; it's a protein named KIM-1, for kidney injury molecule-1. It is a protein that is a membrane glycoprotein known for a long time because it has already been analyzed to be associated with the diagnosis of clear cell RCC vs benign RCC tumors, for instance. It also has been investigated in the blood in the ASSURE trial (NCT00326898). This was a trial led many years ago, which investigated the role of TKIs, sunitinib or sorafenib, vs placebo. In this dataset many years ago, the authors were able to demonstrate that high KIM-1 level in the blood was associated with worse disease-free survival and worse overall survival. This potential circulating biomarker is of interest because it is stable, can be dosed both in the serum or in the plasma, and it's very stable. So, it is a good candidate for circulating blood biomarker.

That led us to move on to the second part of our analysis. Part 2 was to look with a high sensitive assay on the sequential blood samples that were collected in the INmotion010 [trial at] baseline, cycle for day 1, and either at time of disease recurrence or at time of treatment discontinuation when there was no disease recurrence. What we were able to establish are different things. The first one [is] we confirmed the prognostic value of KIM-1. Overall, in INmotion010, patients with high KIM-1 clearly had a higher risk of recurrence. So, this is a prognostic circulating biomarker. Second information is that KIM-1 seems to also carry some predictive value. Indeed, patients who received atezolizumab had a better disease-free survival than those who received placebo. So, this biomarker could speak to its potential predictive value. Third, on treatment assessment of KIM-1, we clearly depict the fact that patients that have an increase on treatment of KIM-1 has worse disease-free survival. So, it could be a monitoring tool in the adjuvant space. And last, we looked at time of recurrence, and here with this more sensitive assay, we confirmed that patients that had disease recurrence had a higher level of KIM-1–about 2-fold higher level than at baseline–while those who did not relapse didn't have an increase in KIM-1.

So taken all together, this is the first time we're having a circulating blood biomarker that could be used as a monitoring tool in the adjuvant space with 3 different aspects. The first one is [it can] assess minimal residual disease. The second one is to define potentially a predictive role of immune checkpoint in the adjuvant setting. And the third one, a monitoring tool to follow-up our patients.

This transcription has been edited for clarity.

Related Videos
Ravi Munver, MD, answers a question during a Zoom video interview
Blur image of hospital corridor | Image Credit: © whyframeshot - stock.adobe.com
Woman having telemedicine appointment with doctor | Image Credit: © Jacob Lund - stock.adobe.com
Daniel Carson, MD, MS, answers a question during a Zoom video interview
Benjamin Pockros, MD, MBA, answers a question during a Zoom video interview
Related Content
© 2024 MJH Life Sciences

All rights reserved.