Evidence map›Paper›PMID 41720427›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2026

Cabozantinib plus nivolumab and ipilimumab in previously untreated, advanced renal cell carcinoma: final results and biomarker analyses from the phase III COSMIC-313 study.

R J Motzer, L Albiges, S A Treviño Aguirre, R Kanesvaran, P Centkowski, M A Reimers, J P Sade, D Pouessel, E Biscaldi, E Esteban and 12 more

Abstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

R J MotzerDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. Electronic address: motzerr@mkscc.org.
L AlbigesMedical Oncology Department, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France.
S A Treviño AguirreiCan Oncology Center S.A. de C.V., Monterrey, Mexico.
R KanesvaranDivision of Medical Oncology, National Cancer Centre Singapore, Singapore.
P CentkowskiKO-MED Centra Kliniczne, Biała Podlaska, Poland.
M A ReimersDivision of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, USA.
J P SadeDepartment of Clinical Oncology, Instituto Alexander Fleming, Buenos Aires, Argentina.
D PouesselDepartment of Medical Oncology, IUCT Oncopole - Oncopole Claudius Régaud, Toulouse, France.
E BiscaldiTranslational Oncology Unit, Istituti Clinici Scientifici Maugeri - IRCCS Pavia, Pavia, Italy.
E EstebanMedical Oncology Department, Central Hospital Universitario Central de Asturias, Oviedo, Spain.
J Á Arranz ArijaMedical Oncology Department, Hospital General Universitario Gregorio Maranon, Madrid, Spain.
S S TykodiDivision of Hematology and Oncology, Department of Medicine, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, USA.
M van Kooten LosioBristol Myers Squibb, Boudry, Neuchâtel, Switzerland.
A DigheCenter of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, USA.
H MaExelixis, Inc., Alameda, USA.
V ValmeekamExelixis, Inc., Alameda, USA.
A SimmonsExelixis, Inc., Alameda, USA.
C ScheffoldExelixis, Inc., Alameda, USA.
S AndrianovaExelixis, Inc., Alameda, USA.
D A BraunCenter of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, USA.
T PowlesBarts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London, UK.
T K ChoueiriLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, USA. Electronic address: toni_choueiri@dfci.harvard.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6M
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2003 to 2026
$53.4M
NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA101942
6 · The paper itself

Abstract

backgroundPrimary results from COSMIC-313 demonstrated significantly longer progression-free survival (PFS) with first-line cabozantinib plus nivolumab and ipilimumab versus placebo plus nivolumab and ipilimumab in patients with advanced renal cell carcinoma. Final efficacy and safety results, as well as data from exploratory biomarker analyses, are reported here. PATIENTS AND

methodsThe design, participants, and primary-endpoint PFS outcomes have been reported previously for this phase III, double-blind, randomized (1 : 1) study of cabozantinib or placebo plus nivolumab and ipilimumab in adults with previously untreated, advanced clear cell renal cell carcinoma. The secondary endpoint was overall survival (OS) in the intention-to-treat population. Exploratory biomarker analyses investigated the potential association between immune cell types and gene signatures with clinical outcomes.

resultsAfter a median follow-up of 45.0 months, the updated median PFS in the cabozantinib (triplet) arm was longer than in the placebo (doublet) arm (16.6 versus 11.2 months; hazard ratio 0.82, 95% confidence interval 0.69-0.98). There was no significant difference in median OS (hazard ratio 1.02, 95% confidence interval 0.85-1.23, P = 0.84), and the safety profile was consistent with the earlier analysis (grade 3/4 treatment-related adverse events occurred in 75% and 43% of patients in the triplet and doublet arms, respectively). In patients with higher levels of M2-like macrophages, the triplet regimen was associated with significantly improved PFS and OS compared with the doublet regimen. Responders in the triplet arm exhibited elevated angiogenic signatures and reduced immune-related pathways, while responders in the doublet arm had robust immune activation.

conclusionsLong-term results from COSMIC-313 continue to demonstrate a PFS benefit with the addition of cabozantinib to nivolumab and ipilimumab. There was no OS benefit and no new safety signals were observed. Exploratory biomarker analyses suggest adding cabozantinib to nivolumab and ipilimumab improves survival in patients with high levels of M2-like macrophages.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Renal CellKidney NeoplasmsAdultAgedAnilidesDouble-Blind MethodFemaleHumansIpilimumabMaleMiddle AgedNivolumabProgression-Free SurvivalPyridinesAnilidesBiomarkers, TumorcabozantinibIpilimumabNivolumabPyridinesbiomarkercabozantinibipilimumabnivolumabphase IIIrenal cell carcinoma

Identifiers

PMID41720427
PMCPMC13463394

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.