BMS-936558 (MDX-1106) In Subjects With Advanced/Metastatic Clear-Cell Renal Cell Carcinoma (RCC)

• ClinicalTrials.gov Identifier: NCT01354431
• Recruitment Status: Active, not recruiting
• First Posted: May 16, 2011
• Results First Posted: October 20, 2015
• Last Update Posted: September 9, 2020
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharma USA Inc
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: May 10, 2011
• First Posted Date: May 16, 2011
• Results First Submitted Date: September 8, 2015
• Results First Posted Date: October 20, 2015
• Last Update Posted Date: September 9, 2020
• Actual Study Start Date: May 17, 2011
• Actual Primary Completion Date: May 15, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 30, 2015)

Median Progression Free Survival (PFS) at Primary Endpoint - Randomized Population [ Time Frame: From randomization until after approximately 116 events (disease progression or death), approximately 2 years. ]

PFS: time from randomization to date of first disease progression (either clinical or radiographic progression, as assessed by the investigator) and measured in Months. Tumor assessments (radiographic scans) were done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression. Survival was assessed every 3 months. The analysis of PFS was conducted after approximately 116 events (progression or death), approximately 2 years. PFS was calculated based on investigator's assessment of first date of progression (either clinical or radiographic progression) or date of death if progression did not occur. Progression was at least a 20% increase in the sum of diameters of the longest target lesions since screening (the sum must be an absolute increase of at least 5 mm), or measurable increase in non-target lesion or appearance of one or more new lesions.

• Original Primary Outcome Measures (submitted: May 13, 2011): Progression free survival as measured by tumor assessments (radiographic scans) and the collection of death data. It will be compared to the doses given across the 3 treatment arms to see if a dose response exists. [ Time Frame: Tumor assessments (radiographic scans) will be done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression is documented. Subjects will be assessed for survival every 3 months. ]

Current Secondary Outcome Measures (submitted: October 30, 2015)

• Objective Response Rate (ORR) at Primary Endpoint- Randomized Population [ Time Frame: From randomization until after approximately 116 events (disease progression or death), approximately 2 years. ]
  Tumor response was evaluated by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Objective response rate (ORR) was defined as the number of responders divided by the number of randomized participants; Responders=complete response (CR) or partial response (PR). CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm; PR: at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR was estimated along with exact 80% Confidence Interval (CI) using the Clopper and Pearson method.
• Number of Participants With Best Overall Response at Primary Endpoint - Randomized Population [ Time Frame: From randomization until after approximately 116 events (disease progression or death), approximately 2 years. ]
  Best response defined as the best response across all time points. Primary endpoint=116 events, approximately 2 years. Tumor response was evaluated by investigator according to RECIST version 1.1. Complete Response (CR): 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): at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease Progression (PD) was at least a 20% increase in the sum of diameters of the longest target lesions since screening (the sum must be an absolute increase of at least 5 mm), or measurable increase in non-target lesion or appearance of one or more new lesions; Stable disease: neither shrinkage to qualify for PR or increase to qualify for PD.
• Median Overall Survival in Months at Interim Data Cut-off - Randomized Population [ Time Frame: From Randomization to approximately 4 years post randomization ]
  Median Overall Survival (OS), measured in months, was based on Kaplan Meier estimates.
• Median Progression Free Survival (PFS) in Months at Interim Data Cut-off - Randomized Population [ Time Frame: From Randomization to approximately 4 years post randomization ]
  PFS: the time from randomization to the date of first disease progression (either clinical or radiographic progression, as assessed by the investigator) was measured in Months. Tumor assessments (radiographic scans) were done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression. PFS was calculated based on investigator's assessment of first date of progression (either clinical or radiographic progression) or date of death if progression did not occur. Participants were censored if they had not experienced disease progression (they were still on treatment or in follow-up) or had received subsequent cancer therapy. Disease Progression was at least a 20% increase in the sum of diameters of the longest target lesions since screening (the sum must be an absolute increase of at least 5 mm), or measurable increase in non-target lesion or appearance of one or more new lesions.

Original Secondary Outcome Measures (submitted: May 13, 2011)

• Progression free survival in the BMS-936558 arms [ Time Frame: Progression free survival will be assessed in each individual treatment arm by tumor assessments every 6 weeks ]
• The tumor response rate in the BMS-936558 arms as assessed by the Investigator assessment of best overall response [ Time Frame: Up to 22 months after study start ]
  The tumor response rate will be assessed on all subjects at the time they discontinue study treatment by the Investigators assessment of best overall response for a subject
• The overall survival in the BMS-936558 arms as collected by death data [ Time Frame: The survival in each treatment arm will be assessed by the collection of death data every 3 months following the discontinuation of study therapy until a subjects death ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: BMS-936558 (MDX-1106) In Subjects With Advanced/Metastatic Clear-Cell Renal Cell Carcinoma (RCC)
• Official Title: A Randomized, Blinded, Phase 2 Dose-Ranging Study Of BMS-936558 (MDX-1106) In Subjects With Progressive, Advanced/Metastatic Clear-Cell Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy
• Brief Summary: The purpose of this study is to measure how active BMS-936558 (nivolumab) is against Renal Cell Carcinoma (RCC) as measured by the disease not progressing and whether a dose response relationship exists.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Renal Cell Carcinoma

Intervention

• Biological: nivolumab
  Solution, Intravenous (IV), 0.3 mg/kg, every 3 weeks (Q 3 weeks), Until Progressive disease (PD), toxicity or discontinue for other reasons
  Other Name: BMS-936558
• Biological: nivolumab
  Solution, Intravenous (IV), 2.0 mg/kg, every 3 weeks (Q 3 weeks), Until Progressive disease (PD), toxicity or discontinue for other reasons
  Other Name: BMS-936558
• Biological: nivolumab
  Solution, Intravenous (IV), 10.0 mg/kg, every 3 weeks (Q 3 weeks), Until Progressive disease (PD), toxicity or discontinue for other reasons
  Other Name: BMS-936558

Study Arms

• Experimental: Arm 1: nivolumab - 0.3 mg/kg
  Intervention: Biological: nivolumab
• Experimental: Arm 2: nivolumab - 2.0 mg/kg
  Intervention: Biological: nivolumab
• Experimental: Arm 3: nivolumab - 10.0 mg/kg
  Intervention: Biological: nivolumab

Publications *

• George S, Motzer RJ, Hammers HJ, Redman BG, Kuzel TM, Tykodi SS, Plimack ER, Jiang J, Waxman IM, Rini BI. Safety and Efficacy of Nivolumab in Patients With Metastatic Renal Cell Carcinoma Treated Beyond Progression: A Subgroup Analysis of a Randomized Clinical Trial. JAMA Oncol. 2016 Sep 1;2(9):1179-86. doi: 10.1001/jamaoncol.2016.0775.
• Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR, Vaishampayan UN, Drabkin HA, George S, Logan TF, Margolin KA, Plimack ER, Lambert AM, Waxman IM, Hammers HJ. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J Clin Oncol. 2015 May 1;33(13):1430-7. doi: 10.1200/JCO.2014.59.0703. Epub 2014 Dec 1.
• George S, Pili R, Carducci MA, Kim JJ. Role of immunotherapy for renal cell cancer in 2011. J Natl Compr Canc Netw. 2011 Sep 1;9(9):1011-8. Review.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 21, 2015): 198
• Original Estimated Enrollment (submitted: May 13, 2011): 150
• Estimated Study Completion Date: November 30, 2020
• Actual Primary Completion Date: May 15, 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Histologic confirmation of Renal cell carcinoma (RCC) with a clear cell component
• Previous treatment with at least one anti-angiogenic agent
• Progressed within 6 months of study enrollment
• Subjects should not have had more than 3 prior treatments for locally advanced or metastatic disease
• Must have available tumor tissue for submission
• Subjects must also meet various laboratory parameters for inclusion

Exclusion Criteria:

• Subjects with any active autoimmune disease or a history of known autoimmune disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Finland, Italy, United States
• Removed Location Countries: Belgium, Spain

Administrative Information

• NCT Number: NCT01354431
• Other Study ID Numbers: CA209-010
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: Bristol-Myers Squibb
• Study Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharma USA Inc

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: August 2020