The investigational imaging agent 89ZR-DFO-girentuximab met all primary and secondary end points, exceeding pre-determined sensitivity and specificity targets in clear cell renal cell carcinoma, according to findings from the phase 3 ZIRCON study.
Topline results from the phase 3 ZIRCON study (NCT03849118) indicated that the investigational PET imaging agent 89ZR-DFO-girentuximab (TLX250-CDx) met every primary and secondary end point in patients with clear cell renal cell carcinoma (RCC), according to a press release from Telix.
In terms of the study’s co-primary end points, use of 89ZR-DFO-girentuximab yielded 86% sensitivity and 87% specificity, respectively. These measures exceeded the pre-determined thresholds to demonstrate the agent’s ability to identify clear cell phenotype as well as presence and spread of disease via non-invasive means. Additionally, the agent met the key secondary end point of sensitivity and specificity in identifying clear cell phenotyping in tumors less than 4 cm, at 85% and 89%, respectively. The agent could provide a solution to significant challenges in identifying clear cell RCC in T1a tumors.
“The positive result from the study is a critical step in better diagnosing clear cell [RCC],” Brian Shuch, MD, director of the Kidney Cancer Program and Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the University of California, Los Angeles Institute of Urologic Oncology, said in the press release. “Having an imaging product like [89ZR-DFO-girentuximab] will be so important in managing the continued increase in incidence of small renal masses and reducing the need for unnecessary invasive surgery for lesions that in the prior era were often found to be benign at the time of surgery."
Investigators of the prospective, open-label, multicenter phase 3 ZIRCON study administered a single dose of 89ZR-DFO-girentuximab to a total of 300 patients, 284 of whom had evaluable results. Histological tumor samples were collected during surgical resection for comparison.
Secondary end points of the study included evaluating the positive predictive value and accuracy of 89ZR-DFO-girentuximab in detecting clear cell RCC in patients with indeterminate solid renal masses and defining a standardized uptake value for the agent suitable for discriminating clear cell from non–clear cell tumors.
Patients 18 years and older who had imaging evidence of a single intermediate renal mass of 7 cm or less in largest diameter with suspicion of clear cell RCC were eligible to enroll on the study. Additional inclusion criteria included being scheduled for lesion resection within 90 days from 89ZR-DFO-girentuximab administration, negative serum pregnancy tests for patients of childbearing potential, sufficient life expectancy to justify nephrectomy, and consent to practice double-barrier contraception for a minimum of 42 days following treatment.
Patients were unsuitable for enrollment if they had a bioptic procedure planned for histological species delineation of indeterminate renal masses or had a renal mass known to be a metastasis of another primary tumor. Patients were also unsuitable for enrollment if they had active non-renal malignancy requiring therapy during the time of the study; had chemotherapy, radiotherapy, or immunotherapy within 4 weeks before treatment administration; or had planned antineoplastic therapies between the time treatment administration and imaging.
Based on the results from the study, a Biologic License Application for 89ZR-DFO-girentuximab will be submitted to the FDA for use in characterizing indeterminate renal masses. Additionally, future uses for the imaging agent may include active surveillance, surgical staging, and treatment response assessments, Françoise Kraeber-Bodéré, MD, PhD, head of the Nuclear Medicine Department at University Hospital of Nantes and Institut de Cancerologie-Gauducheau Cancer Center, concluded.
Telix announces positive topline results of ZIRCON phase 3 kidney cancer imaging study. News release. Telix Pharmaceuticals. November 6, 2022. Accessed November 8, 2022. https://yhoo.it/3NOIzzW