Jad Chahoud, MD, on first-line zanzalintinib plus nivolumab for advanced ccRCC

The combination of zanzalintinib plus nivolumab (Opdivo) demonstrated encouraging preliminary activity with manageable safety in patients with previously-untreated advanced or metastatic clear cell renal cell carcinoma (ccRCC), according to data from an expansion cohort of the phase 1b STELLAR-002 trial (NCT05176483)presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.¹

In a recent interview with Urology Times®, presenting author Jad Chahoud, MD, MPH, MHA, walked through key findings from the interim analysis of the data. Chahoud is a genitourinary medical oncologist at Moffitt Cancer Center in Tampa, Florida.

Overall, treatment with zanzalintinib plus nivolumab was associated with an objective response rate (ORR) of 63%, a disease control rate (DCR) of 90%, and a median progression-free survival (PFS) of 18.5 months. In patients who received zanzalitinib plus nivolumab and relatlimab, the ORR was 40%, the DCR was 90%, and the median PFS was 13 months.

Chahoud noted, “The median PFS may be a bit different because of the median follow-up time for both arms; the doublet arm had a longer median follow-up time because of the sequential enrollment.”

In the doublet arm, 83.4% and 64.4% of patients were free from progression at 6- and 12-months, respectively. In the triplet arm, 80.4% and 58.4% of patients were free from progression at those same time points.

Both the doublet and triplet regimens were generally well-tolerated.

Chahoud added, “We only had 2 grade 4 [adverse events] in each of those arms. Also, we had a low rate of what we call PPE, [or] what we what patients may know as hand-foot syndrome. This is a very bothersome side effect that's very typical for all of these TKIs that are FDA approved currently.”

REFERENCE

1. Chahoud J, McGregor B, Reig O, et al. Zanzalintinib (zanza) + nivolumab (nivo) ± relatlimab (rela) in patients (pts) with previously untreated clear cell renal cell carcinoma (ccRCC): Results from an expansion cohort of the phase 1b STELLAR-002 study. J Clin Oncol. 2025;43(suppl 17):4515. doi:10.1200/JCO.2025.43.16_suppl.4515