ESMO 2024 Kidney Preview: TiNivo-2, SUNNIFORECAST, CheckMate 9ER, and More

In anticipation of the ESMO 2024 Congress, Katy Beckermann, MD, PhD, of Vanderbilt-Ingram Cancer Center, previews various clinical trials and studies to be presented, including those on immunotherapy for metastatic kidney cancer, HIF inhibition, treatments for non-clear cell kidney cancer, and novel biomarkers for predicting treatment responses.

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Dr. Beckermann: I am excited to see the updated data that will be presented at ESMO 2024, and I wanted to highlight some of the presentations I am looking forward to exploring in detail. From a clinical trial standpoint, there are many exciting studies, but I will highlight three.

First, we have been asking since the data was presented from CONTACT-03 if continuing immunotherapy after a patient with metastatic kidney cancer is something we should be doing. Many practitioners in the community have been doing this. From CONTACT-03, where we looked at switching to atezolizumab, a PD-L1 inhibitor, there are questions about whether moving from PD-1 to PD-L1 would be helpful. CONTACT-03, a negative trial, showed that adding atezolizumab to cabozantinib did not provide a benefit and actually increased toxicity compared to cabozantinib alone. This leaves questions about the effectiveness of PD-L1 versus PD-1 agents.

Dr. Toni Choueiri will present the TiNivo-2 study, which will help answer this question. It uses nivolumab, a PD-1 checkpoint inhibitor, in combination with tivozanib, which is approved in the refractory setting for metastatic kidney cancer, and compares it to tivozanib alone. This randomized clinical trial, conducted worldwide, will help determine if PD-1 inhibition after frontline checkpoint inhibition is beneficial. Although a press release from AVEO indicated that the trial did not meet its primary endpoint, I look forward to Dr. Choueiri’s presentation to see how this data might influence clinical practice and treatment sequencing after frontline immunotherapy.

There will also be 2 other presentations that will answer additional questions. Over the last year, we have seen several presentations about HIF inhibition. From the randomized phase 3 study comparing belzutifan versus everolimus, and its recent FDA approval in December 2023, we know there was an improvement in progression-free survival (PFS). Dr. Brian Rini will present the final data update on this at ESMO 2024, and I am eager to see the overall survival data and updated numbers to better understand how HIF inhibition is working in patients with refractory disease who have had prior TKI therapy.

Dr. Eric Jonasch will present a novel HIF inhibitor, NKT2152, from a phase 1/2 study targeting HIF inhibition in a different way. This study looks at patients with refractory disease who have been previously treated. I am interested to see the data, including PFS and objective response rates, to further understand the benefits of HIF inhibition in metastatic kidney cancer.

Another study I am excited to see is for patients with non-clear cell kidney cancer, where it is challenging to perform large, randomized phase 3 clinical trials. Often, we rely on data from other trials. There has been significant effort in a clinical trial called SUNNIFORCAST, a randomized phase 2 trial that includes patients with both papillary and non-papillary kidney cancer. The trial is stratified based on subtype histology and IMDC criteria, and patients are randomized to receive ipi/nivo versus the standard of care. The primary endpoint is overall survival at 12 months. The trial aims to enroll 306 patients, and the initial analysis was planned after the first 200 patients. I look forward to seeing the results of this important study in a rare patient population.

Additionally, there is a phase 2 trial from Italy on fecal microbiota transplantation versus placebo in combination with pembrolizumab and axitinib. As this microbiota story continues to develop, I am interested to see what this trial reveals.

Lastly, I am passionate about biomarker development and understanding predictive and prognostic biomarkers. Dr. David Braun’s name on the schedule always excites me, and he will be presenting on novel serum glycoproteomic biomarkers to predict response to nivo/cabo from the CheckMate-9ER trial. I am eager to learn more about these biomarkers and how they can advance the field.

I hope to dive into all these details and presentations after the meeting.