Investigational imaging agent holds promise for diagnosing renal cancer

In the pivotal phase III ZIRCON study, PET/CT imaging with ⁸⁹Zr-DFO-girentuximab, an investigational imaging agent, demonstrated potential in the noninvasive identification of clear-cell renal cell carcinoma (ccRCC) in patients with indeterminate renal masses (IDRM).

“Our study has met its primary endpoint, exceeding the sensitivity and specificity targets by all three independent readers, [and] its key secondary endpoint of sensitivity and specificity in small masses (cT1a ≤4 cm),” said principal investigator Professor Dr Peter Mulders from Radboud University Medical Centre, Nijmegen, The Netherlands, at EAU 2023.

Sensitivity was 85.5 percent, while specificity was 87 percent. The positive and negative predictive value were 93 percent and 75 percent, respectively. Accuracy was 86 percent. [EAU 2023, abstract LB05]

For small renal lesions, sensitivity and specificity were 85.5 percent and 89.5 percent, respectively. The respective positive and negative predictive values were 93.4 percent and 78 percent, while accuracy was 87 percent.

A total of 124 participants reported 263 treatment-emergent adverse events (TEAEs), but very few were deemed possibly related to ⁸⁹Zr-DFO-girentuximab. Most AEs were mild, with only 6 percent having grade ≥3 TEAEs.

An unmet need

“It is difficult to distinguish between benign and malignant renal masses,” said Mulders. Of the different types of kidney cancer, ccRCC is the most common and aggressive form, he added. Renal mass biopsies are invasive, and up to a third of resected small renal masses are eventually found to be benign. [J Urol 2016;195:1340-1347; Imaging Med 2011;3:207-218]

These factors underpin the importance of advanced imaging for diagnosis and staging to avoid invasive biopsy or surgery to confirm a diagnosis. [telixpharma.com/our-portfolio/disease-areas/kidney-cancer, accessed April 10, 2023] “There is an unmet need in the noninvasive diagnosis and characterization of ccRCC,” Mulders stressed.

The ZIRCON cohort comprised individuals scheduled for partial or radical nephrectomy due to IDRM. On day 0, 300 patients (median age 62 years, 71 percent male) received a single dose of IV ⁸⁹Zr-DFO-girentuximab (37 MBq ± 10 percent; 10 mg girentuximab), which contains the chimeric monoclonal antibody girentuximab that is attached to zirconium-89, a radioactive isotope. This, in turn, produces a signal that is readable on a PET scanner.

The imaging agent targets carbonic anhydrase IX (CAIX), a type of protein highly expressed in ccRCC cells. “CAIX is minimally expressed in normal tissue,” said Mulder. Its presence may then be used to ascertain if a renal mass is ccRCC.

Abdominal PET/CT imaging was done 5 days after the administration of ⁸⁹Zr-DFO-girentuximab. About half of the cohort had small renal masses. Of those with evaluable histopathologic samples (n=288), 67 percent were found to have ccRCC.

A standard diagnostic tool for renal masses?

The findings confirm the potential of ⁸⁹Zr-DFO-girentuximab to become a standard diagnostic modality for IDRM, Mulders said. “[Our] new data reinforce [its] clinical potential … even in small renal masses which are most prevalent and present the highest diagnostic challenge, with remarkable consistency across readers.”

“[Our findings show that] ⁸⁹Zr-DFO-girentuximab has the potential to improve management [of patients with IDRM] by aiding risk stratification, selecting appropriate patients for treatment, or suggesting where further imaging/biopsy could be indicated,” he continued.

This imaging agent also holds promise in improving ccRCC staging, as a therapeutic target, or for identifying other solid tumours. “These are all ongoing initiatives,”­ said Mulder.

Plans are underway to secure regulatory approvals for ⁸⁹Zr-DFO-girentuximab to be a PET/CT imaging agent to further characterize IDRM that has been previously identified on CT or MRI as ccRCC or non-ccRCC. [telixpharma.com/our-portfolio/disease-areas/kidney-cancer, accessed April 10, 2023]