A Study to Test Combination Treatments in People With Advanced Renal Cell Carcinoma (FRACTION-RCC)

A Phase 2, Real-time Assessment of Combination Therapies in Immuno-Oncology Study in Participants With Advanced Renal Cell Carcinoma (FRACTION-RCC)

The purpose of this study is to test the effectiveness and safety of various nivolumab combinations compared to nivolumab and ipilimumab in participants with advanced kidney cancer

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Biological: Nivolumab; Biological: Ipilimumab; Biological: Relatlimab; Drug: BMS-986205; Drug: BMS-813160

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0032
  • Victoria
    • Bentleigh, Victoria, Australia, 3165
      • Monash Medical Centre Clayton
• Austria
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4010
      • Local Institution - 0044
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Local Institution - 0038
    • Oshawa, Ontario, Canada, L1G 2B9
      • Local Institution - 0029
    • Toronto, Ontario, Canada, M5G 1Z6
      • Local Institution - 0035
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution - 0034
    • Québec, Quebec, Canada, G1R 2J6
      • Local Institution - 0030
• Israel
  • Haifa, Israel, 3109601
    • Local Institution
  • Ramat Gan, Israel, 52621
    • Local Institution
• Italy
  • Milano, Italy, 20133
    • Local Institution - 0010
  • Napoli, Italy, 80131
    • Local Institution - 0012
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0037
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • Local Institution
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Local Institution - 0031
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Local Institution - 0006
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0007
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Local Institution - 0011
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Local Institution - 0008
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Local Institution - 0005
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0043
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Local Institution - 0014
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 0002
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0025
  • Texas
    • Dallas, Texas, United States, 75390-8570
      • UT Southwestern Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Local Institution - 0024
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington - Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Advanced Renal Cell Carcinoma
• Must have at least 1 lesion with measurable disease
• Life expectancy of at least 3 months
• Karnofsky Performance Status (KPS) must be =>70%

Exclusion Criteria:

• Patients/subjects with suspected or known central nervous system metastases unless adequately treated
• Patients/subjects with autoimmune disease
• Patients/subjects who need daily oxygen therapy

Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nivolumab + Ipilimumab	Biological: Nivolumab; Specified Dose on Specified Days; Other Names: BMS-936558; Opdivo; Biological: Ipilimumab; Specified Dose on Specified Days; Other Names: BMS-734016; Yervoy
Experimental: Nivolumab + Relatlimab	Biological: Nivolumab; Specified Dose on Specified Days; Other Names: BMS-936558; Opdivo; Biological: Relatlimab; Specified Dose on Specified Days; Other Names: BMS-986016
Experimental: Nivolumab + BMS-986205	Biological: Nivolumab; Specified Dose on Specified Days; Other Names: BMS-936558; Opdivo; Drug: BMS-986205; Specified Dose on Specified Days
Experimental: Nivolumab + BMS-813160; Nivolumab + BMS-813160 (CCR2/5 dual antagonist)	Biological: Nivolumab; Specified Dose on Specified Days; Other Names: BMS-936558; Opdivo; Drug: BMS-813160; Specified Dose on Specified Days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Investigator	ORR is percent of participants whose best overall response (BOR) is complete response (CR) or partial response (PR). BOR is the best response from the start of the study treatment until objectively documented progression per RECIST v1.1 or subsequent anticancer therapy, whichever occurs first. For participants who received re-treatment or were re-randomized, the re-treatment and re-randomized therapies were considered subsequent anticancer therapy. CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The Response Evaluation Criteria in Solid Tumors (RECIST) is a standard way to measure the response of a tumor to treatment. CR+PR, confidence interval based on Clopper and Pearson method.	From first dose of study treatment until progression or subsequent anticancer therapy, whichever occurs first (assessed up to approximately 247 weeks)
Median Duration of Response (DOR) Per Investigator	Duration of Response is defined as the time between the date of first response and the date of first documented disease progression as determined by RECIST 1.1 or death due to any cause (death occurring after re-treatment or randomization to new combination treatment was not considered), whichever occurred first. Complete Response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Median computed using Kaplan -Meier method	From first dose to the date of first documented disease progression or death due to any cause (assessed from an average of 22 weeks up to approximately 247 weeks)
Progression Free Survival Rate (PFSR) at 24 Weeks.	The PFSR at 24 weeks is defined as the proportion of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, 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). Point estimates are derived from Kaplan-Meier analyses, the 95% CIs are derived from Greenwood formula	24 weeks after first treatment dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From first dose to 100 days after last dose of study therapy (assessed up to approximately 118 weeks)
Number of Participants With Serious Adverse Events (SAEs)	Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization	From first dose to 100 days after last dose of study therapy (assessed up to approximately 118 weeks)
Number of Participants With Adverse Events (AEs) Leading to Discontinuation	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From first dose to 100 days after last dose of study therapy (assessed up to approximately 118 weeks)
Number of Participants Who Died	Death is defined as the cessation of all vital functions of the body including the heartbeat, brain activity (including the brain stem), and breathing.	From first dose to 100 days after last dose of study therapy (assessed up to approximately 118 weeks)
Number of Participants With Abnormal Thyroid Test Results - Track 1	The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal.	From first dose to 30 days after last dose of study therapy (approximately 108 weeks)
Number of Participants With Abnormal Thyroid Test Results - Track 2	The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal	From first dose to 30 days after last dose of study therapy (approximately 108 weeks)
Number of Participants With Abnormal Hepatic Test Results - Track 1	The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal	From first dose to 30 days after last dose of study therapy (approximately 108 weeks)
Number of Participants With Abnormal Hepatic Test Results - Track 2	The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal	From first dose to 30 days after last dose of study therapy (approximately 108 weeks)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Choueiri TK, Kluger H, George S, Tykodi SS, Kuzel TM, Perets R, Nair S, Procopio G, Carducci MA, Castonguay V, Folefac E, Lee CH, Hotte SJ, Miller WH Jr, Saggi SS, Lee CW, Desilva H, Bhagavatheeswaran P, Motzer RJ, Escudier B. FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy. J Immunother Cancer. 2022 Nov;10(11):e005780. doi: 10.1136/jitc-2022-005780.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): November 23, 2021
• Study Completion (Actual): November 23, 2021

Study Registration Dates

• First Submitted: December 15, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimate): December 19, 2016

Study Record Updates

• Last Update Posted (Actual): December 19, 2022
• Last Update Submitted That Met QC Criteria: November 18, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab; Linrodostat
• Other Study ID Numbers: CA018-005; 2016-003082-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No