A Phase 3 interventional study of Cabozantinib and Nivolumab in Renal Cell Carcinoma, sponsored by Exelixis. Active, not recruiting at 159 sites in 25 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-09-10.
Sponsored by Exelixis · Phase 3, Interventional, and Treatment
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.
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. The primary objective of this study is to evaluate the effect of cabozantinib in combination with nivolumab and ipilimumab ("triplet") on the duration of progression-free survival (PFS) versus nivolumab and ipilimumab. A secondary objective is to evaluate the effect of triplet combination on the duration of overall survival (OS).
1,965 studies on the registry are indexed under Carcinoma, Renal Cell; 378 are open to participants now.
This study's enrollment of 855 is above the median of 42 across 1,480 interventional studies indexed under Carcinoma, Renal Cell.
Browse Carcinoma, Renal Cell studies →Exelixis is the lead sponsor of 57 studies on the registry; 12 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Other clinically significant disorders such as:
Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
Drug: Cabozantinib · Biological: Nivolumab · Biological: Ipilimumab
Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab
Biological: Nivolumab · Biological: Ipilimumab · Drug: Cabozantinib-matched placebo
Specified dose on specified days.
Also known as: Cabometyx, XL184
Specified dose on specified days.
Also known as: Opdivo, BMS-936558
Specified dose on specified days.
Also known as: Yervoy, BMS-734016
Specified dose on specified days.
Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC)
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.
Time frame: Up to 32 months
Duration of Overall Survival (OS)
Duration of OS (months) = (earliest date of death or censoring - date of randomization + 1)/30.4375.
Time frame: Up to 58 months
| Milestone | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab |
|---|---|---|
| Started | 428 | 427 |
| Received at least 1 dose of study drug | 426 | 423 |
| Progression free survival (pfs) intent-to-treat (pitt) population | 276 | 274 |
| Safety analysis set | 426 | 423 |
| Intent to treat (itt) population | 428 | 427 |
| Completed | 185 | 187 |
| Not completed | 243 | 240 |
| Withdrew: Death | 223 | 211 |
| Withdrew: Withdrawal by subject | 17 | 25 |
| Withdrew: Lost to follow-up | 3 | 4 |
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.
| months | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab |
|---|---|---|
| Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC) | NA (14.00 to NA) | 11.30 (7.69 to 18.17) |
Duration of OS (months) = (earliest date of death or censoring - date of randomization + 1)/30.4375.
| months | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab |
|---|---|---|
| Duration of Overall Survival (OS) | 41.86 (34.79 to 47.87) | 41.99 (34.92 to 53.13) |
Collected over Day 1 up to 58 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cabozantinib + Nivolumab + Ipilimumab | 224/426 (52.6%) | 272/426 (63.8%) | 421/426 (98.8%) |
| Placebo + Nivolumab + Ipilimumab | 217/423 (51.3%) | 257/423 (60.8%) | 416/423 (98.3%) |
| Event | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab |
|---|---|---|
| Alanine aminotransferase increasedInvestigations | 45/426 | 11/423 |
| Aspartate aminotransferase increasedInvestigations | 34/426 | 13/423 |
| Immune-mediated hepatitisHepatobiliary disorders | 20/426 | 3/423 |
| DiarrhoeaGastrointestinal disorders | 14/426 | 17/423 |
| COVID-19Infections and infestations | 16/426 | 17/423 |
| Renal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 13/426 | 15/423 |
| PneumoniaInfections and infestations | 13/426 | 10/423 |
| Adrenal insufficiencyEndocrine disorders | 11/426 | 12/423 |
| ColitisGastrointestinal disorders | 5/426 | 10/423 |
| VomitingGastrointestinal disorders | 2/426 | 9/423 |
| Event | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 216/426 | 108/423 |
| Alanine aminotransferase increasedInvestigations | 204/426 | 89/423 |
| Aspartate aminotransferase increasedInvestigations | 195/426 | 74/423 |
| FatigueGeneral disorders | 133/426 | 129/423 |
| PruritusSkin and subcutaneous tissue disorders | 106/426 | 131/423 |
| HypertensionVascular disorders | 125/426 | 45/423 |
| Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders | 123/426 | 26/423 |
| HypothyroidismEndocrine disorders | 122/426 | 81/423 |
| Decreased appetiteMetabolism and nutrition disorders | 118/426 | 84/423 |
| NauseaGastrointestinal disorders | 112/426 | 105/423 |
The Intent-to-Treat (ITT) population was defined as all randomized participants regardless of whether any study treatment or the correct study treatment was received.
| Age, Categorical(Participants) | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 277 | 276 | 553 |
| >=65 years | 151 | 151 | 302 |
| Sex: Female, Male(Participants) | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab | Total |
|---|---|---|---|
| Female | 102 | 115 | 217 |
| Male | 326 | 312 | 638 |
| Ethnicity (NIH/OMB)(Participants) | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab | Total |
|---|---|---|---|
| Hispanic or Latino | 130 | 127 | 257 |
| Not Hispanic or Latino | 263 | 273 | 536 |
| Unknown or Not Reported | 35 | 27 | 62 |
| Race (NIH/OMB)(Participants) | Cabozantinib + Nivolumab + Ipilimumab | Placebo + Nivolumab + Ipilimumab | Total |
|---|---|---|---|
| American Indian or Alaska Native | 4 | 10 | 14 |
| Asian | 29 | 33 | 62 |
| Native Hawaiian or Other Pacific Islander | 0 | 2 | 2 |
| Black or African American | 3 | 6 | 9 |
| White | 339 | 331 | 670 |
| More than one race | 2 | 2 | 4 |
| Unknown or Not Reported | 51 | 43 | 94 |
Showing the first 100 of 159 sites across 25 countries.
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This study is active, not recruiting, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.
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