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Neoadjuvant nivolumab

Phase 3

Renal Cell Carcinoma | Small molecule | Oncology |Bristol-Myers Squibb Company|Last Updated: Aug 24, 2026

Target and mechanism

Molecular targetPDCD1
Target classInhibitor
ModalitySmall molecule

Also known as Nivolumab, Nivolumab Injection [Opdivo], Opdivo, nivolumab, Nivolumab and rHuPH20, nivolumab 480mg, Nivolumab 480mg and relatlimab 160mg, Nivolumab and relatlimab

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials8
Total Enrollment1,822

FDA Designations

BREAKTHROUGH_THERAPYPRIORITY_REVIEW

Clinical trial landscape

Neoadjuvant nivolumab · 8 trials · 2 indications

Phase 3 2Phase 2 3Phase 1 3
NCT03873402A Study of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Participants With Advanced Kidney CancerRenal Cell Carcinoma
ACTIVE NOT_RECRUITING437 Analytics
NCT03141177A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell CarcinomaRenal Cell Carcinoma
COMPLETED701 Analytics
PHASE3ACTIVE NOT_RECRUITING
A Study of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Participants With Advanced Kidney Cancer
Renal Cell CarcinomaUnlock trial analytics
PHASE3COMPLETED
A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
Renal Cell CarcinomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression free survival (PFS) by blinded independent central review (BICR)
Up to 34 months
Objective response rate (ORR) by BICR
Up to 23 months
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

Pathologic response rate
At 6 weeks

Pathologic response rate is defined as the proportion of patients demonstrating a complete pathologic or partial pathologic response, according to central revision (pathology of NKI)

The Percentage of Participant With Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Within 2 Days After Any Dose in the Combination Period
From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)

The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).

Incidence of adverse events (AEs) by severity (Part 1)
Up to 2.5 years
Incidence of serious adverse events (SAEs) (Part 1)
Up to 2.5 years
Incidence of dose-limiting toxicities (DLTs) (Part 1)
Up to 2.5 years
Incidence of AEs leading to discontinuation (Part 1)
Up to 5 years
Incidence of immune-mediated adverse events (imAEs) (Part 1)
Up to 5 years
Incidence of changes in clinical laboratory results by severity: Hematology tests (Part 1)
Up to 2.5 years
Incidence of changes in clinical laboratory results by severity: Clinical Chemistry tests (Part 1)
Up to 2.5 years
Incidence of changes in clinical laboratory results by severity: Urinalysis tests (Part 1)
Up to 2.5 years
Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation
From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)

Safety assessments by treatment arm and dose level were based on incidence of AEs, and the incidence of serious adverse events (SAEs). AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.

Percent Change From Baseline in Activated and Memory T Cells
Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1

The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody in activated and memory T cells with metastatic clear-cell Renal Cell Carcinoma (RCC)

Mean Serum Cytokines: CXCL9
Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months)

Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)

Mean Serum Cytokines CXCL10 (IP10)
Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months)

Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)

Mean CD4 T Cell Infiltration
Cycle 2 Day 8 168 Hr post dose

The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD4 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC).

Mean CD8 T Cell Infiltration
168 hour post does Cycle 2 Day 8 in evaluable participates (First active dose of study medication to cycle two day eight post injection)

The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD8 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC).

Secondary Endpoints

Overall survival (OS)
Up to 4 years
Overall response rate (ORR) by investigator
Up to 4 years
Disease control rate (DCR) by investigator
Up to 4 years
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Nivolumab + ipilimumabEXPERIMENTAL -
Nivolumab + ipilimumab placeboEXPERIMENTAL -
DoubletEXPERIMENTALNivolumab and Cabozantinib
MonotherapyACTIVE_COMPARATORSunitinib
TripletEXPERIMENTALNivolumab, Ipilimumab, Cabozantinib \*Enrollment to the triplet arm was discontinued by protocol amendment
A: Neoadjuvant nivolumabEXPERIMENTALNeoadjuvant 2 cycles of nivolumab 360mg every 3 weeks
B: Neoadjuvant nivolumab + ipilimumabEXPERIMENTALNeoadjuvant 2 cycles of nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks
C: Neoadjuvant nivolumab + relatlimabEXPERIMENTALNeoadjuvant 2 cycles of nivolumab 360mg + relatlimab 360mg every 3 weeks
Co-AdministrationEXPERIMENTALNivolumab and Ipilimumab Co-Administration
Sequential AdministrationEXPERIMENTALNivolumab and Ipilimumab Sequential Administration
Arm 1: nivolumab - 0.3 mg/kgEXPERIMENTAL -
Arm 2: nivolumab - 2.0 mg/kgEXPERIMENTAL -
Arm 3: nivolumab - 10.0 mg/kgEXPERIMENTAL -
Part 1A (Part 1): Nivolumab + AxitinibEXPERIMENTAL -
Part 1B (Part 1): Nivolumab + CabozantinibEXPERIMENTAL -
Arm S: Nivolumab + SunitinibEXPERIMENTALNivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons Sunitinib 50 mg capsule by mouth on Days 1-28 of 42 day cycle until Progressive disease (PD), toxicity or discontinue for other reasons
Arm P: Nivolumab + PazopanibEXPERIMENTALNivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons Pazopanib 800 mg tablet by mouth daily until Progressive disease (PD), toxicity or discontinue for other reasons
Arm I-1: Nivolumab + IpilimumabEXPERIMENTALNivolumab 3 mg/kg solution intravenously (IV) every 21 days during Induction phase and every 14 days during Maintenance phase until Progressive disease (PD), toxicity or discontinue for other reasons Ipilimumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase (Ipilimumab will not be administered during Maintenance phase) until Progressive disease (PD), toxicity or discontinue for other reasons
Arm I-3: Nivolumab + IpilimumabEXPERIMENTALNivolumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase
Arm IN-3: Nivolumab+IpilimumabEXPERIMENTALNivolumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase
Arm 1: BMS-936558EXPERIMENTAL -
Arm 2: BMS-936558EXPERIMENTAL -
Arm 3: BMS-936558EXPERIMENTAL -
Arm 4: BMS-936558EXPERIMENTAL(treatment naive)

Interventions

NameTypeDescription
NivolumabBIOLOGICALSpecified dose on specified days
IpilimumabBIOLOGICALSpecified dose on specified days
Ipilimumab placeboOTHERSpecified dose on specified days
CabozantinibDRUGSpecified dose on specified days
SunitinibDRUGSpecified dose on specified days.
Neoadjuvant nivolumabDRUGPatients will receive 2 cycles of nivolumab 360mg (arm A and C) or 3mg/kg (arm B) every 3 weeks followed by a nephrectomy.
Neoadjuvant ipilimumabDRUGPatients will receive 2 cycles of ipilimumab 1mg/kg every 3 weeks followed by a nephrectomy.
Neoadjuvant relatlimabDRUGPatients will receive 2 cycles of relatlimab 360mg every 3 weeks followed by a nephrectomy.
OpdivoBIOLOGICALSpecified dose on specified days
YervoyBIOLOGICALSpecified dose on specified days
AxitinibDRUGSpecified dose on specified days
PazopanibBIOLOGICAL -
BMS-936558 (Anti-PD-1)DRUGSolution, Intravenous infusion, 0.3 mg/kg, Every 3 weeks, Indefinitely depending on response
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites78

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Histological confirmation of renal carcinoma with clear cell component including participants who may have sarcomatoid features. * Advanced (not amenable to ...

Countries:United StatesArgentinaAustriaChileCzechiaFranceGreeceItalyMexicoPolandPortugalRomaniaRussiaSpainAustraliaBrazilGermanyIsraelJapanTurkey (Türkiye)United KingdomNetherlandsCanadaFinland
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Recent Changes (Last 90 Days)

HIGHAug 24, 2026NCT03141177Status: ACTIVE_NOT_RECRUITING → COMPLETED
HIGHAug 24, 2026NCT03141177Status: ACTIVE_NOT_RECRUITING → COMPLETED

Frequently asked questions about Neoadjuvant nivolumab

What is BMS-936558 used for?

BMS-936558, also known as nivolumab and marketed as Opdivo, is an investigational oncology drug being studied for advanced or metastatic melanoma, non-squamous cell non-small cell lung cancer, localized oesogastric adenocarcinoma, follicular lymphoma, cancer, and gastric cancer. It is developed by Bristol-Myers Squibb Company (BMY) and is currently in Phase 1 clinical development.

What does BMS-936558 target?

BMS-936558 is a monoclonal antibody (target class -mab) that targets the programmed cell death protein 1 (PD-1) receptor. By binding to PD-1, it is designed to enhance the immune system's ability to fight cancer cells. This mechanism is being evaluated across multiple oncology indications.

Who makes BMS-936558?

BMS-936558 is developed by Bristol-Myers Squibb Company, a biopharmaceutical company traded on the New York Stock Exchange under the ticker BMY. The drug is also known as nivolumab and is marketed under the brand name Opdivo.

What phase is BMS-936558 in?

BMS-936558 is currently in Phase 1 clinical development. It has received FDA breakthrough therapy designation and priority review status. The drug is investigational and not yet approved, with ongoing clinical trials evaluating its safety and efficacy in various cancer types.

What clinical trials is BMS-936558 in?

BMS-936558 has been studied in multiple clinical trials, including NCT02741570, a Phase 3 trial in head and neck cancer, and NCT02823574, a Phase 2 trial in the same condition. Other trials include NCT03355560 and NCT03894891, both Phase 2 studies in head and neck cancer. Across 14 trials, total enrollment is 6,828 patients.

Is BMS-936558 the same as Opdivo?

Yes, BMS-936558 is the same as Opdivo. The drug is also known as nivolumab, nivolumab injection, and nivolumab 10 mg/ml. It is being developed by Bristol-Myers Squibb and is currently in Phase 1 trials for multiple oncology indications.