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NCT03937219: COSMIC-313

Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

Active, enrolled Phase 3 Results posted Last updated 10 September 2025
What this trial tests

Phase 3 trial testing Cabozantinib in Renal Cell Carcinoma in 855 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
25 June 2019
Primary endpoint
31 January 2022
31 January 2027

Quick facts

Lead sponsorExelixis
PhasePhase 3
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment855
Start date25 June 2019
Primary completion31 January 2022
Estimated completion31 January 2027
Sites159 locations across Hong Kong, Italy, Finland, Taiwan, Poland, South Korea, New Zealand, Netherlands

Drugs / interventions tested

Conditions studied

Sponsor

Exelixis — full company profile →

Who can join

18 and older, any sex, with Renal Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC) Primary · Up to 32 months

Duration of PFS was defined as the time from randomization to the earlier of either the date of radiographic progression per BIRC or the date of death due to any cause. PFS (months) = (earliest date of progression, death, censoring - date of randomization + 1)/30.4375. PFS was determined as per Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1.

GroupValue95% CI
Cabozantinib + Nivolumab + IpilimumabNA14.00 – NA
Placebo + Nivolumab + Ipilimumab11.307.69 – 18.17
Duration of Overall Survival (OS) Secondary · Up to 58 months

Duration of OS (months) = (earliest date of death or censoring - date of randomization + 1)/30.4375.

GroupValue95% CI
Cabozantinib + Nivolumab + Ipilimumab41.8634.79 – 47.87
Placebo + Nivolumab + Ipilimumab41.9934.92 – 53.13

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 up to 58 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cabozantinib + Nivolumab + Ipilimumab
Serious: 272/426 (64%)
Deaths: 224/426
Placebo + Nivolumab + Ipilimumab
Serious: 257/423 (61%)
Deaths: 217/423

Serious adverse events (347 terms)

ReactionSystemCabozantinib + Nivolumab +…Placebo + Nivolumab + Ipil…
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Immune-mediated hepatitisHepatobiliary disorders
DiarrhoeaGastrointestinal disorders
COVID-19Infections and infestations
Renal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumoniaInfections and infestations
Adrenal insufficiencyEndocrine disorders
ColitisGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HyponatraemiaMetabolism and nutrition disorders
Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumonitisRespiratory, thoracic and mediastinal disorders
HypophysitisEndocrine disorders
HypertransaminasaemiaHepatobiliary disorders
HypercalcaemiaMetabolism and nutrition disorders
Pathological fractureMusculoskeletal and connective tissue disorders
Acute kidney injuryRenal and urinary disorders
Deep vein thrombosisVascular disorders
Acute myocardial infarctionCardiac disorders
Atrial fibrillationCardiac disorders
Immune-mediated enterocolitisGastrointestinal disorders
General physical health deteriorationGeneral disorders
Other adverse events (63 terms — click to expand)

ReactionSystemCabozantinib + Nivolumab +…Placebo + Nivolumab + Ipil…
DiarrhoeaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
FatigueGeneral disorders
PruritusSkin and subcutaneous tissue disorders
HypertensionVascular disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Decreased appetiteMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Lipase increasedInvestigations
RashSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
Amylase increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Abdominal painGastrointestinal disorders
HeadacheNervous system disorders
StomatitisGastrointestinal disorders
Blood creatinine increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
COVID-19Infections and infestations
DysphoniaRespiratory, thoracic and mediastinal disorders
HyperthyroidismEndocrine disorders
Mucosal inflammationGeneral disorders
Weight decreasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Gamma-glutamyltransferase increasedInvestigations
Blood bilirubin increasedInvestigations
DysgeusiaNervous system disorders
DyspepsiaGastrointestinal disorders
Oedema peripheralGeneral disorders
InsomniaPsychiatric disorders

Most-reported serious reactions: Alanine aminotransferase increased, Aspartate aminotransferase increased, Immune-mediated hepatitis, Diarrhoea, COVID-19, Renal cell carcinoma, Pneumonia, Adrenal insufficiency.

Data from ClinicalTrials.gov NCT03937219 adverse events section.

Sponsor's own description

This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio at approximately 180 sites.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial.
    Motzer RJ, Powles T, Burotto M, Escudier B, et al · · 2022 · cited 238× · PMID 35688173 · DOI 10.1016/s1470-2045(22)00290-x
  2. Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities.
    Hack SP, Zhu AX, Wang Y. · · 2020 · cited 223× · PMID 33250900 · DOI 10.3389/fimmu.2020.598877
  3. Immunotherapy in Renal Cell Carcinoma: The Future Is Now.
    Deleuze A, Saout J, Dugay F, Peyronnet B, et al · · 2020 · cited 178× · PMID 32260578 · DOI 10.3390/ijms21072532
  4. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma.
    Choueiri TK, Powles T, Albiges L, Burotto M, et al · · 2023 · cited 117× · PMID 37163623 · DOI 10.1056/nejmoa2212851
  5. Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma.
    Rassy E, Flippot R, Albiges L. · · 2020 · cited 110× · PMID 32215057 · DOI 10.1177/1758835920907504
  6. Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors.
    Apolo AB, Nadal R, Girardi DM, Niglio SA, et al · · 2020 · cited 96× · PMID 32915679 · DOI 10.1200/jco.20.01652
  7. Combination of Ipilimumab and Nivolumab in Cancers: From Clinical Practice to Ongoing Clinical Trials.
    Kooshkaki O, Derakhshani A, Hosseinkhani N, Torabi M, et al · · 2020 · cited 95× · PMID 32580338 · DOI 10.3390/ijms21124427
  8. The role of MET in chemotherapy resistance.
    Wood GE, Hockings H, Hilton DM, Kermorgant S. · · 2021 · cited 78× · PMID 33526881 · DOI 10.1038/s41388-020-01577-5

Verify or expand the search:

Other trials of Cabozantinib

Trials testing the same drug.

Other recruiting trials for Renal Cell Carcinoma

Currently open trials in the same condition.

Other Exelixis trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03937219.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing