Dr Chahoud on Early Efficacy With Zanzalintinib Plus Nivolumab With/Without Relatlimab in ccRCC

"[We saw a] very deep, active response [with this regimen] that appears to be durable. Three-quarters of patients are still on study and in response, as of the data cutoff."

Jad Chahoud, MD, MPH, MHA, an associate member in the Department of Genitourinary Oncology and medical director of IPOP at Moffitt Cancer Center, discussed results from the dose-expansion cohort of the phase 1b STELLAR-002 study (NCT05176483), which evaluated zanzalintinib plus nivolumab (Opdivo) with or without relatlimab-rmbw (Opdualag) in patients with previously untreated clear cell renal cell carcinoma (ccRCC).

In the dose-escalation cohort, the investigators identified the recommended dose and assessed safety, Chahoud stated. Initial signals of activity were observed not only in patients with ccRCC but also in those with prostate and colorectal cancers, which informed the decision to advance into the dose-expansion cohorts, Chahoud explained.

At the 2025 ASCO Annual Meeting, findings from the ccRCC cohort were presented. The zanzalintinib plus nivolumab doublet demonstrated an overall response rate (ORR) of 63% (95% CI, 46%-77%), comprised of an 8% complete response rate (CR) and 55% partial response rate (PR), Chahoud reported. One additional patient achieved a confirmed PR after the data cutoff, increasing the ORR to approximately 65%, Chahoud added.

In contrast, the triplet arm comprised of zanzalintinib plus nivolumab plus relatlimab showed a lower ORR of 40% (95% CI, 25%-57%), including 3% CR and 38% PR rates, Chahoud stated. At the time of the data cutoff, 5 patients in this arm had unconfirmed partial responses that may convert upon longer follow-up, he noted.

The doublet cohort had a longer median follow-up of 20.1 months compared with 15.9 months for the triplet cohort, Chahoud reported. The disease control rate was 90% (95% CI, 76%-97%) in both arms. The median time to treatment response was 2.1 months (range, 1.7-11.0) in the doublet arm and 3.6 months (range, 1.7-12.8) in the triplet cohort, Chahoud emphasized.

Regarding duration of response, the 12-month duration of response rate was 73.4% (95% CI, 50.0%-87.1%) with the doublet and 74.1% (95% CI, 39.1%-90.9%) with the triplet, Chahoud stated.