Shuchi Gulati, MD, reviewed current imaging techniques for renal cell carcinoma (RCC) to provide background for the presentation by Michael Hofman, MBBS, on novel imaging tools. Dr. Gulat’s key points were that imaging in RCC is central to staging, therapy selection, and response assessment, so it is imperative to know when to use each modality. New imaging modalities must be validated in clinical trials.
Dr. Hofman reviewed the history of imaging in RCC, anticipating advances in PET tracers specifically targeting the carbonic anhydrase 9 (CA-IX or Ca9) receptor, which is over-expressed in clear cell (cc) RCC. He drew analogies with targeting the prostate-specific membrane antigen (PSMA in prostate cancer, which has revolutionized care via theranostics (therapy plus diagnostics) using radioisotopes to first image and then treat tumors via the same molecular target.
PET tracers that are specific and sensitive for targeting the CA9 receptor are in development. Dr. Hofman said, “I think the peptides are going to win [over antibodies] with earlier imaging, less background noise, actually much higher tumor uptake.”
The gadolinium 68-labeled Ca9-targeting peptide DPI-4452 used in PET/CT has visualized primary ccRCC tumors as small as 4 mm, and can detect bone metastases. Clinical trials of this agent are ongoing. Other Ca9-targeting tracers are in clinical trials, including some in combination with immunotherapies, although side effects and off-target uptake may complicate development.
Hans Hammers, MD, PhD, reviewed novel targets in kidney cancer. He predicts a proliferation of novel combination therapies at various disease stages with the promise of higher efficacy but also toxicity. These include inhibitors like belzutifan, which targets hypoxia-inducible factor-2 and is approved for von Hippel-Lindau (VHL) disease; bispecific T-cell engagers (BiTE); CAR-T cell therapies, particularly off-the-shelf allogeneic ones; novel small molecules that can be administered orally; and individualized mRNA vaccines.
Dr. Hammers said, “I am a big believer in personalized vaccines, so I hope that this will be something that will move forward.” Individualized mRNA vaccines targeting patient-specific tumor mutations have shown significant activity in melanoma and are in trial in other cancer types. However no trials of mRNA vaccines for kidney cancer are currently listed in clinicaltrials.gov.
Pavlos Msaouel, MD, PhD, talked about the use of Bayesian Optimal Interval (BOIN) Design in clinical trials of drug and biological products, which the FDA has designated “fit-for-purpose” for phase 1 dose-finding trials. He said the BOIN Software Suite, simple and free for anyone to use, is available through www.trialdesign.org. He described the application of the BOIN and BOP2 suites in phase 1 and 2 trials, respectively, in kidney cancer trial designs.
The session concluded with a presentation of results of CYTOSHRINK: a randomized phase 2 trial of cytoreductive stereotactic hypofractionated radiotherapy (SBRT) with ipilimumab/nivolumab for metastatic kidney cancer. There no significant difference in progression-free survival between arms. Presenter Aly-Khan Lalani, MD, said that was probably due to patients in the SBRT arm having much more advanced disease.
Dr. Lederman has no conflicts of interest to report.
Image by Palii Yurii / Shutterstock
