A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

A Phase 3, Randomized, Open-Label Study of Nivolumab Combined With Cabozantinib Versus Sunitinib in Participants With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03141177

Acronym

CheckMate 9ER

Enrollment

701

Registered

2017-05-04

Start date

2017-07-23

Completion date

2026-04-01

Last updated

2026-08-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Renal Cell Carcinoma

Brief summary

The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in previously untreated advanced or metastatic renal cell carcinoma

Interventions

BIOLOGICALNivolumab

Specified dose on specified day

DRUGCabozantinib

Specified dose on specified days

DRUGSunitinib

Specified dose on specified days.

BIOLOGICALIpilimumab

Specified dose on specified days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Histological confirmation of RCC with a clear-cell component, including participants who may also have sarcomatoid features * Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC * No prior systemic therapy for RCC with the following exception: i) One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets VEGF or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy

Exclusion criteria

* Any active CNS metastases * Any active, known or suspected autoimmune disease * Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization * Participants who have received a live/attenuated vaccine within 30 days of first treatment Other protocol defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Progression Free Survival (PFS)	From randomization date to date of first documented tumor progression or death, whichever occurs first (Up to 31 months)	PFS is defined as the time from date of randomization to the first documented tumor progression date or death due to any cause, whichever occurs first based on BICR assessment using RECIST v1.1. Participants who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment on or prior to initiation of subsequent anti-cancer therapy. Progressive disease (PD); 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study

Secondary

Measure	Time frame	Description
Overall Survival (OS)	From randomization date to death date (Up to 31 months)	Overall Survival is defined as the time between the date of randomization and the date of death due to any cause. For participants that are alive, their survival time will be censored at the date of last contact date (or "last known alive date").
Objective Response Rate (ORR)	Up to 31 Months	Objective Response Rate (ORR) is defined as the percentage of randomized participants who achieve a best response of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1 criteria) divided by the number of all randomized participants. Complete response (CR): Disappearance of all target lesions. Partial response (PR): 30% decrease in the sum of diameters of target lesions.
Number of Participants Experiencing Adverse Events (AEs)	From first dose to 100 days following last dose (Up to 32 Months)	Number of participants experiencing various types of any grade adverse events (AEs) during the specified time frame.
Number of Participants Experiencing Serious Adverse Events (SAEs)	From first to dose to 100 days following last dose (Up to 32 months)	Number of participants experiencing various types of any grade serious adverse events (SAEs) during the specified time frame.
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation	From first dose to 30 days following last dose (Up to 30 months)	Number of participants experiencing various types of any grade adverse events (AEs) leading to discontinuation during the specified time frame.
Number of Deaths	From first dose to (up to 31 months) following first dose	Number of deaths due to any cause during the specified time frame.
Number of Participants With Laboratory Values Grade Shifting From Baseline	From first dose to 30 days following last dose (Up to 30 Months)	Number of participants experiencing worsening shift from baseline in any grade and grade 3-4 of laboratory values during the specified time frame.
Number of Participants With Laboratory Abnormalities	From first dose to 30 days following last dose (Up to 30 Months)	Number of participants experiencing laboratory abnormalities in hematology, serum chemistry and electrolytes with grade 3 or higher during the specified time frame.

Countries

Argentina, Australia, Brazil, Chile, Czechia, Germany, Greece, Israel, Italy, Japan, Mexico, Poland, Romania, Russia, Spain, Turkey (Türkiye), United Kingdom, United States

Contacts

STUDY_DIRECTORBristol-Myers Squibb

Bristol-Myers Squibb

Participant flow

Pre-assignment details

701 participants randomized and 690 treated.

Participants by arm

Arm	Count
Treatment A Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD	323
Treatment B Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses) Then Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD	50
Treatment C Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle	328
Total	701

Baseline characteristics

Characteristic	Treatment A	Treatment B	Treatment C	Total
Age, Continuous	61.4 Years STANDARD_DEVIATION 10.2	60.3 Years STANDARD_DEVIATION 9.5	60.4 Years STANDARD_DEVIATION 10.6	60.9 Years STANDARD_DEVIATION 10.4
Ethnicity (NIH/OMB) Hispanic or Latino	38 Participants	13 Participants	39 Participants	90 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	149 Participants	19 Participants	151 Participants	319 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	136 Participants	18 Participants	138 Participants	292 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants	0 Participants	2 Participants	5 Participants
Race (NIH/OMB) Asian	26 Participants	0 Participants	25 Participants	51 Participants
Race (NIH/OMB) Black or African American	1 Participants	0 Participants	4 Participants	5 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	26 Participants	7 Participants	31 Participants	64 Participants
Race (NIH/OMB) White	267 Participants	43 Participants	266 Participants	576 Participants
Sex: Female, Male Female	74 Participants	16 Participants	96 Participants	186 Participants
Sex: Female, Male Male	249 Participants	34 Participants	232 Participants	515 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	67 / 320	14 / 50	99 / 320
other Total, other adverse events	316 / 320	48 / 50	306 / 320
serious Total, serious adverse events	160 / 320	28 / 50	144 / 320

Outcome results

Primary

Progression Free Survival (PFS)

PFS is defined as the time from date of randomization to the first documented tumor progression date or death due to any cause, whichever occurs first based on BICR assessment using RECIST v1.1. Participants who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment on or prior to initiation of subsequent anti-cancer therapy. Progressive disease (PD); 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study

Time frame: From randomization date to date of first documented tumor progression or death, whichever occurs first (Up to 31 months)

Population: All Randomized Participants of treatment A and treatment C

Arm	Measure	Value (MEDIAN)
Treatment A	Progression Free Survival (PFS)	16.59 Months
Treatment C	Progression Free Survival (PFS)	8.31 Months

p-value: <0.000195% CI: [0.41, 0.64]Stratified Log-Rank

Secondary