- Zanzalintinib in combination with nivolumab demonstrated an objective response rate of 63% and a disease control rate of 90%
- Additional results from dose-finding cohorts will also be presented
“We are pleased to present these preliminary findings from the phase 1b/2 STELLAR-002 study, including early signs of promising activity for zanzalintinib in combination with immune checkpoint inhibitors,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “Data emerging from this ongoing study are important to help inform further evaluation of zanzalintinib-based regimens in advanced solid tumors, including renal cell carcinoma.”Abstract 4515: Zanzalintinib + Nivolumab ± Relatlimab in Patients with Previously Untreated Clear Cell Renal Cell Carcinoma: Results from an Expansion Cohort of the Phase 1b STELLAR-002 Study
Lead Author: Jad Chahoud, M.D., M.P.H., Moffitt Cancer Center, Tampa, Fla., USA
Session Title: Genitourinary Cancer—Kidney and Bladder
Saturday, May 31, 1:15-2:45 p.m. CDT
This expansion cohort of STELLAR-002 included patients with advanced clear cell RCC who received zanzalintinib in combination with either nivolumab (n=40) or fixed-dose nivolumab and relatlimab (n=40) in two non-randomized treatment arms. Patients had unresectable advanced or metastatic disease for which they received no prior systemic therapy. Intermediate- or poor-risk disease, per the International Metastatic RCC Database Consortium, accounted for 75% of patients receiving zanzalintinib in combination with nivolumab and 70% of patients receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab.
At a median follow-up of 20.1 months for those receiving zanzalintinib in combination with nivolumab and 15.9 months for those receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab, the objective response rates were 63% (95% confidence interval [CI]: 46-77%) and 40% (95% CI: 25-57%), respectively. Disease control rates were 90% (95% CI: 76-97%) for both arms. The 12-month duration of response was 73.4% (95% CI: 50.0-87.1%) and 74.1% (95% CI: 39.1-90.9%), respectively. Median progression-free survival was 18.5 months (95% CI: 9.5 months-not estimable [NE]) and 13.0 months (95% CI: 7.4 months-NE), respectively.
“While significant progress has been made in advanced clear cell renal cell carcinoma, many patients still experience disease progression, and more effective therapies earlier in the treatment landscape are needed,” said Jad Chahoud, M.D., M.P.H., Associate Member, Department of Genitourinary Oncology and Medical Director of the Inpatient/Outpatient (IPOP) service at Moffitt Cancer Center in Tampa, Fla., who is presenting the findings. “The high rate of durable responses and long progression-free survival observed for zanzalintinib in combination with nivolumab are encouraging and support further evaluation of this regimen.”
Treatment-emergent adverse events (TEAEs) of any grade were reported in all patients. Grade 3/4 TEAEs occurring in at least four patients receiving zanzalintinib in combination with nivolumab included hypertension (n=13), diarrhea (n=6), aspartate aminotransferase increase (n=5), alanine aminotransferase increase (n=5) and palmar-plantar erythrodysesthesia (n=4). Grade 3/4 TEAEs occurring in at least four patients receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab included hypertension (n=6), rash (n=6), lipase increase (n=4) and pulmonary embolism (n=4). There were two grade 5 TEAEs in each arm; none were considered related to study treatment. Three patients (8%) in the zanzalintinib in combination with nivolumab arm and eight patients (20%) in the zanzalintinib in combination with fixed-dose nivolumab and relatlimab arm discontinued all study drugs for treatment-related AEs as assessed by investigator.
Abstract 3101: Zanzalintinib + Nivolumab ± Relatlimab in Patients with Advanced Solid Tumors: Results from Two Dose-Escalation Cohorts of the Phase 1b STELLAR 002 Study
Lead Author: Benjamin Garmezy, M.D., Sarah Cannon Research Institute, Nashville, Tenn., USA
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Monday, June 2, 1:30-4:30 p.m. CDT
This analysis of STELLAR-002 included multiple cohorts of patients with advanced solid tumors who received zanzalintinib 100 mg in combination with nivolumab (n=19); zanzalintinib 60 mg in combination with fixed-dose nivolumab and relatlimab (n=24); or zanzalintinib 100 mg in combination with fixed-dose nivolumab and relatlimab (n=25). The most common cancer types for those receiving zanzalintinib in combination with nivolumab were colorectal and prostate cancers, followed by lung cancer and RCC. The most common tumor types in the zanzalintinib in combination with fixed-dose nivolumab and relatlimab cohorts were RCC, followed by prostate cancer, melanoma and colorectal cancer.
The findings showed that the toxicity profile of these combinations was manageable and consistent with each monotherapy agent. Preliminary safety, efficacy and pharmacokinetic results supported selection of the 100 mg dose for zanzalintinib for the ongoing expansion cohorts.
Source: Exelixis, Inc. (2025). Exelixis Announces Encouraging Results from Phase 1b/2 STELLAR-002 Trial Evaluating Zanzalintinib in Combination with Immune Checkpoint Inhibitors in Advanced Kidney Cancer at ASCO 2025 [Press release]. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-encouraging-results-phase-1b2-stellar-002.