A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advanced or Has Spread

NCT04810078 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: CA209-67T2020-003655-15U1111-1255-9514
• Study Type: interventional
• Target: 681
• Locations: 17 countries
• Sites: 89

Brief Summary

The purpose of this study is to evaluate the drug levels, efficacy, safety, and tolerability of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread. The purpose of this study's substudy is to evaluate drug level biocomparability of subcutaneous nivolumab manufactured using two different manufacturing processes.

Conditions

Clear Cell Renal Cell Carcinoma

Keywords

BMS-936558; BMS-986298; Clear cell renal cell carcinoma; ccRCC; Nivolumab; Opdivo; rHuPH20; Subcutaneous

Outcome Measures

Primary Outcomes (2)

• Adjusted Geometric Mean Serum Concentration of Nivolumab Over 28 Days (Cavgd28) on Original Scale

  Plasma samples were collected to assess the serum concentration.

  Pre-dose (Day 1 to Day 28)

• Adjusted Geometric Mean of Nivolumab Trough Serum Concentration at Steady State (Cminss) on Original Scale

  Plasma samples were collected to assess the serum concentration.

  Pre-dose (Day 1 to Day 28)

Secondary Outcomes (16)

• Objective Response Rate (ORR) Per BICR

  From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 26 months)

• Trough Serum Concentration of Nivolumab at Day 28 (Cmind28)

  Pre-dose at Day 28

• Maximum Serum Concentration of Nivolumab After the First Dose (Cmax1)

  Post dose (Day 1)

• Peak Serum Concentration of Nivolumab at Steady State (Cmaxss)

  Pre-dose (Day 1 to Day 28)

• Time-averaged Serum Concentration of Nivolumab at Steady State (Cavgss)

  Pre-dose (Day 1 to Day 28)

Study Arms (4)

Arm A

EXPERIMENTAL

Biological: Nivolumab and rHuPH20

Arm B

ACTIVE COMPARATOR

Biological: Nivolumab

Arm C

EXPERIMENTAL

Biological: Nivolumab and rHuPH20

Arm D

EXPERIMENTAL

Biological: Nivolumab and rHuPH20

Interventions

Nivolumab and rHuPH20 BIOLOGICAL

Specified dose on specified days

Also known as: BMS-986298

Arm A; Arm C; Arm D

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo, BMS-936558

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of renal cell carcinoma (RCC) with a clear cell component, including participants who may also have sarcomatoid features
• Advanced RCC (not amenable to curative surgery or radiation therapy) or metastatic RCC (Stage IV)
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 criteria within 28 days prior to randomization
• Received no more than 2 prior systemic treatment regimens
• Intolerance or progression on or after the last treatment regimen received and within 6 months prior to randomization
• Karnofsky PS ≥ 70 at screening
• Must agree to follow specific methods of contraception, if applicable

You may not qualify if:

• Untreated, symptomatic central nervous system (CNS) metastases
• Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to randomization
• Active, known, or suspected autoimmune disease
• Known human immunodeficiency virus (HIV) positive with an acquired immunodeficiency syndrome (AIDS) defining opportunistic infection within the last year, or a current CD4 count \< 350 cells/μL. Participants with HIV are eligible if:
• They have received established antiretroviral therapy (ART) for at least 4 weeks prior to randomization
• They continue on ART as clinically indicated while enrolled on study
• CD4 counts and viral load are monitored per standard of care by a local health care provider
• Serious or uncontrolled medical disorders including for example, active severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) infection within approximately 4 weeks prior to screening. In the case of prior SARS-CoV-2 infection, acute symptoms must have resolved based on investigator clinical judgment and, in consultation with Medical Monitor, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment to be eligible
• Prior treatment with an programmed death receptor-1 (anti-PD-1), programmed death ligand-1 (anti-PD-L1), or cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways
• Treatment with any live attenuated vaccine within 30 days of first study treatment

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (89)

Local Institution

Chicago, Illinois, 60611, United States

Location

Local Institution - 0025

Buffalo, New York, 14263, United States

Location

Local Institution - 0088

West Reading, Pennsylvania, 19611, United States

Location

Local Institution - 0038

Buenos Aires, Buenos Aires, C1426ANZ, Argentina

Location

Local Institution - 0095

Capital Federal, Buenos Aires, C1419AHN, Argentina

Location

Local Institution - 0058

Mar del Plata, Buenos Aires, 7600, Argentina

Location

Local Institution - 0037

Pergamino, Buenos Aires, B2700CPM, Argentina

Location

Local Institution - 0079

Parana, Córdoba Province, 5000, Argentina

Location

Local Institution - 0030

Río Cuarto, Córdoba Province, 5800, Argentina

Location

Local Institution - 0066

Viedma, Río Negro Province, R8500ACE, Argentina

Location

Local Institution - 0056

San Juan, San Juan Province, J5402DIL, Argentina

Location

Local Institution - 0064

Curitiba, Paraná, 80520-174, Brazil

Location

Local Institution - 0090

Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

Location

Local Institution - 0107

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Local Institution - 0039

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Local Institution - 0071

Barretos, São Paulo, 014784-000, Brazil

Location

Local Institution - 0070

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Local Institution - 0081

São Paulo, São Paulo, 01246-000, Brazil

Location

Local Institution - 0096

São Paulo, São Paulo, 01327-0001, Brazil

Location

Local Institution - 0084

Temuco, Araucania, Chile

Location

Local Institution - 0005

Santiago, Santiago Metropolitan, 0, Chile

Location

Local Institution - 0104

Santiago, Santiago Metropolitan, 7500653, Chile

Location

Local Institution - 0076

Santiago, Santiago Metropolitan, 7500921, Chile

Location

Local Institution - 0077

Viña del Mar, Valparaiso, 2520598, Chile

Location

Local Institution - 0063

Brno, 656 53, Czechia

Location

Local Institution - 0036

Hradec Králové, 500 05, Czechia

Location

Local Institution - 0020

Olomouc, 77900, Czechia

Location

Local Institution - 0099

Ostrava, 708 52, Czechia

Location

Local Institution - 0010

Prague, 140 59, Czechia

Location

Local Institution - 0106

Praha 8 Liben, 18081, Czechia

Location

Local Institution - 0017

Tampere, 33521, Finland

Location

Local Institution

Nice, 6189, France

Location

Local Institution - 0051

Suresnes, 92151, France

Location

Local Institution - 0068

Villejuif, 94800, France

Location

Local Institution - 0060

Tallaght, Dublin, 0, Ireland

Location

Local Institution - 0033

Cremona, 26100, Italy

Location

Local Institution - 0008

Florence, 50134, Italy

Location

Local Institution - 0027

Meldola, 47014, Italy

Location

Local Institution - 0018

Milan, 20141, Italy

Location

Local Institution

Milan, 20133, Italy

Location

Local Institution - 0014

Padova, 35128, Italy

Location

Local Institution - 0082

Parma, 43126, Italy

Location

Local Institution - 0092

Pavia, 27100, Italy

Location

Local Institution - 0100

Roma, 00168, Italy

Location

Local Institution - 0091

Rome, 00152, Italy

Location

Local Institution - 0057

Terni, 05100, Italy

Location

Local Institution - 0101

Torreón, Coahuila, 27010, Mexico

Location

Local Institution - 0089

Tlalpan, Mexico City, 14080, Mexico

Location

Local Institution - 0103

Monterrey, Nuevo León, 64460, Mexico

Location

Local Institution - 0031

Monterrey, Nuevo León, 64710, Mexico

Location

Local Institution - 0065

Querétaro City, Querétaro, 76000, Mexico

Location

Local Institution - 0085

Querétaro City, Querétaro, 76090, Mexico

Location

Local Institution - 0105

San Luis Potosí City, San Luis Potosí, 78200, Mexico

Location

Local Institution - 0053

Auckland, 1023, New Zealand

Location

Local Institution - 0041

Hamilton, 3204, New Zealand

Location

Local Institution - 0078

Palmerston North, 4414, New Zealand

Location

Local Institution - 0055

Biała Podlaska, 21-500, Poland

Location

Local Institution - 0062

Bydgoszcz, 85-796, Poland

Location

Local Institution - 0083

Gdansk, 80-214, Poland

Location

Local Institution - 0021

Krakow, 30-688, Poland

Location

Local Institution - 0098

Krakow, 31-115, Poland

Location

Local Institution - 0001

Poznan, 60-569, Poland

Location

Local Institution - 0023

Warsaw, 02-781, Poland

Location

Local Institution - 0050

Coimbra, 3030-075, Portugal

Location

Local Institution - 0052

Lisbon, 1500-650, Portugal

Location

Local Institution - 0024

Bucharest, 022238, Romania

Location

Local Institution - 0002

Cluj-Napoca, 400132, Romania

Location

Local Institution - 0040

Cluj-Napoca, 400641, Romania

Location

Local Institution - 0016

Craiova, 200347, Romania

Location

SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine

Chelyabinsk, 454087, Russia

Location

Ivanovo Regional Oncology Dispensary

Ivanovo, 153040, Russia

Location

Hertzen Moscow Oncology Research Center

Moscow, 125284, Russia

Location

Local Institution

Nizghiy Novgorod, 603000, Russia

Location

Budgetary Healthcare Institution of Omsk Region - Clinical Oncological Dispensary

Omsk, 644013, Russia

Location

LLC Eurocityclinic

Saint Petersburg, 197022, Russia

Location

Local Institution - 0048

Barcelona, 08003, Spain

Location

Local Institution - 0102

Barcelona, 08035, Spain

Location

Local Institution - 0049

Barcelona, 08041, Spain

Location

Local Institution - 0072

Madrid, 28026, Spain

Location

Local Institution - 0067

Madrid, 28033, Spain

Location

Local Institution - 0074

Madrid, 28046, Spain

Location

Local Institution - 0075

Madrid, 28050, Spain

Location

Local Institution - 0032

Sabadell, 08208, Spain

Location

Local Institution - 0086

Santander, 39008, Spain

Location

Local Institution - 0059

Seville, 31013, Spain

Location

Local Institution - 0035

Istanbul, Bagcilar, 34284, Turkey (Türkiye)

Location

Local Institution - 0026

Ankara, 06230, Turkey (Türkiye)

Location

Local Institution - 0097

Ankara, 06590, Turkey (Türkiye)

Location

Local Institution - 0019

Istanbul, 34098, Turkey (Türkiye)

Location

Related Publications (1)

• Albiges L, Bourlon MT, Chacon M, Cutuli HJ, Chuken YAL, Zurawski B, Mota JM, Magri I, Burotto M, Luz M, de Menezes J, Ruiz EPY, Fu S, Richardet M, Valderrama BP, Maruzzo M, Bracarda S, Breckenridge M, Vezina HE, Rathod D, Yu Z, Zhao Y, Dixon M, Perumal D, George S. Subcutaneous versus intravenous nivolumab for renal cell carcinoma. Ann Oncol. 2025 Jan;36(1):99-107. doi: 10.1016/j.annonc.2024.09.002. Epub 2024 Sep 15.

  PMID: 39288844 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 22, 2021
• Study Start: May 21, 2021
• Primary Completion: July 29, 2025
• Study Completion (Estimated): May 10, 2027
• Last Updated: September 22, 2026
• Results First Posted: September 22, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (3); PL (7); RO (4); FR (3); CZ (6); ES (10); PT (2); IE (1); TU (4); AR (8); CL (5); FI (1); BR (8); NZ (3); RU (6); ME (7); IT (11)