KEY TAKEAWAYS
- Phase 3 ZIRCON trial was aimed at exploring a precise noninvasive method to detect ccRCC by using radiolabeled 89Zr-DFO-girentuximab to target the CAIX enzyme strongly expressed in ccRCC.
- The Primary Outcome Measure evaluated the sensitivity and specificity of qualitative PET/CT imaging assessment to detect and identify IDRM.
- The study demonstrated that the TLX250-CDx could safely and precisely detect ccRCC and can potentially be developed the best treatment plans for IDRM patients.
Phase 3 ZIRCON study aimed to detect ccRCC in adult patients with undetermined renal masses as a precise noninvasive method to direct patient care.
A monoclonal antibody called girentuximab targets the enzyme carbonic anhydrase IX (CAIX), strongly expressed in clear cell renal carcinoma (ccRCC). Because it is extremely specific for CAIX, radiolabeled 89Zr-DFO-girentuximab (TLX250-CDx) can help distinguish between ccRCCs and other renal lesions.
Patients with indeterminate renal masses (IDRM) (7 cm; tumor stage cT1) who had a partial nephrectomy slated within 90 days of the intended administration of TLX250-CDx were eligible. Enrolled patients got PET/CT imaging on Day 5 (about two days before surgery) and a single dose of TLX250-CDx IV (37 MBq 10%; 10 mg girentuximab) on Day 0.
The status of the ccRCC was established by a blinded central histology review. The co-primary goals were to assess the sensitivity and specificity of TLX250-CDx PET/CT imaging in detecting ccRCC. Additional auxiliary goals were positive and negative predictive values, safety, and tolerability.
A total of 300 patients were given TLX250-CDx; their average age was 62 years and 12 months, and 71% of them were men. About 193 (67%) of the 288 individuals whose surgical samples had central histopathology had ccRCC, and 179 (62%) had CT1a; The average across all 3 readers for sensitivity and specificity for the 284 evaluable patients included in the main analysis was 86% [80%, 90%] and 87% [79%, 92%] for co-primary endpoints; and 85% [77%, 91%] and 90% [79%, 95%] respectively for key secondary endpoints.
The co-primary and important secondary endpoints’ lower 95% confidence interval limits for all readers were > 75%. Positive and negative predictive values were 91.7% and 73.7%, respectively, for all evaluable cases. Treatment-emergent adverse events (TEAEs), 2 TEAEs were treatment-related.
According to this research, TLX250-CDx PET/CT is safe to use, can detect ccRCC accurately and noninvasively, and can potentially be useful in developing the best treatment plans for IDRM patients.
Source: https://meetings.asco.org/abstracts-presentations/216521
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03849118
Shuch B. M., Pantuck A. J., Bernhard J. C., Morris M. A., Master V. A., Scott A. M., Praet C. V., Bailly C., Aksoy T., Merkx R., Schuster D. M., Lee S. T., Pandit-Taskar N., Fan A. C., Tauchmanova L., Allman P., Vadali K., Hayward C. & Mulders P. (2023).
Results from phase 3 study of 89Zr-DFO-girentuximab for PET/CT imaging of clear cell renal cell carcinoma (ZIRCON). J Clin Oncol 41, 2023 (suppl 6; abstr LBA602) DOI: 10.1200/JCO.2023.41.6_suppl.LBA602
