An Investigational Immuno-Therapy Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma (CheckMate 800)

• ClinicalTrials.gov Identifier: NCT03029780
• Recruitment Status: Completed
• First Posted: January 24, 2017
• Results First Posted: December 19, 2018
• Last Update Posted: June 29, 2022
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

Brief Summary:

The purpose of this study is to evaluate safety and efficacy of different administration regimens of nivolumab plus ipilimumab in subjects with renal cell carcinoma.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma	Biological: Opdivo; Biological: Yervoy	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Randomized, Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma
• Actual Study Start Date: February 16, 2017
• Actual Primary Completion Date: November 27, 2017
• Actual Study Completion Date: June 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Co-Administration; Nivolumab and Ipilimumab Co-Administration	Biological: Opdivo; Specified dose on specified days; Other Name: Nivolumab; Biological: Yervoy; Specified dose on specified days; Other Name: Ipilimumab
Experimental: Sequential Administration; Nivolumab and Ipilimumab Sequential Administration	Biological: Opdivo; Specified dose on specified days; Other Name: Nivolumab; Biological: Yervoy; Specified dose on specified days; Other Name: Ipilimumab

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 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).

Secondary Outcome Measures :

1. The Percentage of Participant With Adverse Events in the Narrow Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Occurring Within 2 Days After Any Dose in the Combination Period [ Time Frame: 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 narrow scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).
2. The Percentage of Participants With Drug Related Grade 3-5 Adverse Events [ Time Frame: From first dose to 30 days after last dose of study therapy (up to approximately 48 months) ]
   The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher, judged to be related to study treatment by the investigator, with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.
3. The Percentage of Participants With All Causality Grade 3-5 Adverse Events [ Time Frame: From first dose to 30 days after last dose of study therapy (up to approximately 48 months) ]
   The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using the NCI CTCAE version 4.0 criteria
4. Objective Response Rate (ORR) [ Time Frame: From randomization to the date of objectively documented progression or the date of first subsequent anti-cancer (up to approximately 52 months) ]
   The percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Complete Response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
5. Progression Free Survival (PFS) [ Time Frame: From randomization to the first date of documented progression or death due to any cause (up to approximately 52 months) ]
   The time between the date of randomization and the first date of documented progression, or death due to any cause, whichever occurs first (per investigator). Participants who die without progression will be considered to have progressed on the date of their death. Participants who did not progress or die are censored on the date of their last evaluable tumor assessment. Participants with no on study tumor assessments and who did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)
6. Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab [ Time Frame: pre-dose on day 1 of cycle 2 and 4 ]
   Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized prior to the next dose (predose). 1 Cycle = 3 weeks
7. Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab [ Time Frame: EOI on day 1 of cycle 1, 2, and 4 ]
   Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized at the end of infusion (EOI). 1 Cycle = 3 weeks

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Advanced Renal Cell Carcinoma
• Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
• Must have at least 1 lesion with measurable disease

Exclusion Criteria:

• Subjects with active central nervous system metastases
• Subjects who received prior therapy with checkpoint inhibitor
• Subjects with active, known or suspected autoimmune disease

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

Locations

United States, Florida

Cancer Specialists of North FL

Jacksonville, Florida, United States, 32256

United States, Iowa

University Of Iowa Hospitals And Clinics

Iowa City, Iowa, United States, 52242

United States, North Carolina

Levine Cancer Institute

Charlotte, North Carolina, United States, 28204

United States, Pennsylvania

Local Institution

Pittsburgh, Pennsylvania, United States, 15212-0000

Australia, New South Wales

Local Institution

Waratah, New South Wales, Australia, 2298

Local Institution

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Local Institution

Herston, Queensland, Australia, 4029

Australia, South Australia

Local Institution

Elizabeth Vale, South Australia, Australia, 5112

Australia, Victoria

Local Institution

Malvern, Victoria, Australia, 3144

Chile

Fundacion Arturo Lopez Perez

Santiago, Metropolitana, Chile, 7500921

Centro Internacional de Estudios Clinicos

Recoleta, Santiago De Chile, Chile

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:

Study Protocol  [PDF] August 2, 2017

Statistical Analysis Plan  [PDF] September 11, 2017

More Information

Additional Information:

BMS Clinical Trial Information 

BMS Clinical Trial Patient Recruiting 

FDA Safety Alerts and Recalls 

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03029780
• Other Study ID Numbers: CA209-800
• First Posted: January 24, 2017
• Results First Posted: December 19, 2018
• Last Update Posted: June 29, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Nivolumab; Ipilimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action