The phase III COSMIC-313 study demonstrated that adding cabozantinib to nivolumab and ipilimumab significantly improved progression-free survival and objective response rate in patients with previously untreated advanced renal cell carcinoma of intermediate or poor risk. Overall survival was similar between the treatment arms. The triplet regimen had a higher rate of grade 3/4 adverse events and treatment discontinuations but no new safety signals were observed. Exploratory biomarker analyses suggest that patients with high levels of M2-like macrophages may benefit more from the triplet combination.
Study
|
International, multicenter, randomized, double-blinded, placebo-controlled, phase III study [COSMIC-313] |
| Previously untreated advanced or metastatic clear cell RCC with IMDC intermediate or poor risk |
| Cabozantinib 40 mg plus nivolumab and ipilimumab (n=428) vs placebo plus nivolumab and ipilimumab (n=427)
|
Efficacy
|
ORR: 46% vs 37% (cabozantinib vs. placebo) |
| mPFS: 16.6 mos vs 11.2 mos (HR 0.82 [0.69-0.98]) |
| 12-mo PFS: 57% vs 48% |
| mOS: 41.9 mos vs 42.0 mos (HR 1.02 [0.85-1.23]) |
| 36-mo OS: 54% vs 54% |
| mDoR: 31.1 mos vs NE
|
Safety
|
Grade 3/4 TRAEs: ALT increased (26% vs 6%), diarrhea (5% vs 3%), PPES (4% vs 0%), hypertension (9% vs 2%), hypothyroidism (<1% vs 0%) |
| Grade 5 TRAEs: 0.7% vs 1.2% |
| Treatment discontinuation due to TRAEs: 49% vs 26% |
| Immune-modulating medications used: 73% vs 57% |
| High-dose corticosteroids used: 59% vs 37%
|
Ann Oncol. Published online 18 February 2026
http://doi.org/10.1016/j.annonc.2026.02.011
Reviewed by Ulas D. Bayraktar, MD on Jun 12, 2026
