Darren Feldman, MD, on study of 177Lu-girentuximab plus nivolumab for ccRCC

The phase 2 STARLITE 2 trial (NCT05239533) is assessing the safety and efficacy of ¹⁷⁷Lu-girentuximab in combination with nivolumab for the treatment of patients with advanced clear cell renal cell carcinoma (ccRCC) that has the CAIX protein.

In a recent interview with Urology Times®, Darren R. Feldman, MD, shared the background/rationale for the trial, which was also presented at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California.¹ Feldman is a GU medical oncologist, associate attending physician, and section head of the germ cell cancer program within the GU oncology service at Memorial Sloan Kettering Cancer Center in New York, New York.

In total, the study plans to enroll 41 patients across 7 clinical trial sites in the US.2 The study will be conducted with a safety lead-in to determine the maximum tolerated dose (MTD) of 177Lu-girentuximab in this patient population. Dosing in this phase will begin at 1804 MBq/m² (75% of single agent MTD), which may be escalated to 2405 MBq/m² (cohort 2; single agent MTD) or de-escalated to 1353 MBq/m² (cohort -1). Once the MTD is determined, the study will proceed to the expansion phase.

The primary end point for the expansion phase is response rate per RECIST v1.1, assessed within 24 weeks. Secondary end points will include progression-free survival, overall survival, and toxicity.

In the study, ⁸⁹Zr-girentuximab PET/CT is used as the tracer for imaging, and ¹⁷⁷Lu-girentuximab is used for the therapeutic. ⁸⁹Zr-DFO-girentuximab is currently under review for approval in the US, with a PDUFA date set for August 27, 2025.³

REFERENCES

1. Feldman DR, Motzer RJ, Knezevic A, et al. STARLITE 2: Phase 2 study of nivolumab plus 177lutetium-labeled anti–carbonic anhydrase IX (CAIX) monoclonal antibody girentuximab (177Lu-girentuximab) in patients with advanced clear cell renal cell carcinoma (ccRCC). Presented at: 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 13-15, 2025. San Francisco, California

2. Study of Nivolumab in Combination with 177Lu-girentuximab for Kidney Cancer. ClinicalTrials.gov. Last updated February 3, 2025. Accessed March 21, 2025. https://clinicaltrials.gov/study/NCT05239533

3. FDA accepts BLA for TLX250-CDx (Zircaix) for kidney cancer imaging, grants priority review. News release. Telix Pharmaceuticals. February 25, 2025. Accessed February 26, 2025. https://telixpharma.com/news-views/fda-accepts-bla-for-tlx250-cdx-zircaix-for-kidney-cancer-imaging-grants-priority-review/