A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)

• ClinicalTrials.gov Identifier: NCT01721746
• Recruitment Status: Completed
• First Posted: November 6, 2012
• Results First Posted: March 22, 2017
• Last Update Posted: April 19, 2022
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: November 2, 2012
• First Posted Date: November 6, 2012
• Results First Submitted Date: February 1, 2017
• Results First Posted Date: March 22, 2017
• Last Update Posted Date: April 19, 2022
• Actual Study Start Date: December 21, 2012
• Actual Primary Completion Date: February 16, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 23, 2022)

• Objective Response Rate (ORR) [ Time Frame: From date of randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (Up to approximately 38 months) ]
  Objective response rate (ORR) per Independent Review Committee (IRC) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized participants using RECIST 1.1
• Overall Survival (OS) [ Time Frame: Up to 96 months ]
  Overall Survival (OS) was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. Unit of measure (months) is the median survival time.

Original Primary Outcome Measures (submitted: November 2, 2012)

• Objective response rate (ORR) of BMS-936558 in subjects with advanced melanoma [ Time Frame: 23 months ]
  ORR is defined as the number of subjects with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized subjects
• Overall survival(OS) of BMS-936558 in subjects with advanced melanoma [ Time Frame: 23 months ]
  Overall Survival (OS) is defined the time between the date of randomization to the date of death

Current Secondary Outcome Measures (submitted: March 23, 2022)

• Progression Free Survival (PFS) [ Time Frame: From the date of randomization to the date of the first documented progression or death (Up to approximately 38 months) ]
  Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented progression, as determined by the Independent Review Committee (IRC) using RECIST 1.1, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment before subsequent anti-cancer therapy. Unit of measure (months) is the median survival time.
• Objective Response Rate (ORR) by Baseline PD-L1 Expression [ Time Frame: From date of randomization to the date of objectively documented progression or the date of subsequent therapy (Up to approximately 38 months) ]
  Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by number of randomized participants. PD-L1 expression evaluated for ORR.
• Overall Survival (OS) by PD-L1 Positive [ Time Frame: Up to 96 months ]
  Overall Survival (OS) by PD-L1 expression was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive.
• Overall Survival (OS) by PD-L1 Negative [ Time Frame: Up to 96 months ]
  Overall Survival (OS) by PD-L1 expression was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive.
• Mean Change From Baseline in Health-related Quality of Life (HRQoL) [ Time Frame: From Baseline (Day1) to second Follow-Up (Up to 96 months) ]
  Health-related Quality of Life (HRQoL) was assessed with the EORTC QLQ-C30 questionnaire, which is the most commonly used quality-of-life instrument in oncology trials. The instrument's 30 items were divided among 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health/quality of life scale. Raw scores for the EORTC QLQ-C30 were transformed to a 0-100 metric. Higher scores for all functional scales and Global Health Status=better HRQoL Increase from baseline indicates improvement in HRQoL. Lower scores for symptom scales=better HRQoL Decline from baseline for symptom scales =improvement in symptoms compared to baseline. A 10 point difference on a 100 point scale between treatments was considered clinically significant.

Original Secondary Outcome Measures (submitted: November 2, 2012)

• Progression-free survival (PFS) [ Time Frame: 23 months ]
  PFS is defined as the time from randomization to the date of the first documented progression or death due to any cause, whichever occurs first
• Programmed death-ligand 1 (PD-L1) expression [ Time Frame: 23 months ]
  To evaluate whether PD-L1 expression is a predictive biomarker for ORR and OS by testing the interaction between PD-L1 expression and treatment arms
• Health Related Quality of Life (HRQoL) [ Time Frame: Baseline (Day1) and 23 months ]
  HRQoL will be measured by mean changes from screening/baseline in the EORTC QLQ-C30 global health status/QoL composite scale and by mean changes from screening/baseline in the remaining EORTC QLQ-C30 scales in all randomized subjects

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

Descriptive Information

• Brief Title: A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)
• Official Title: A Randomized Open-Label Phase 3 Trial of BMS-936558 (Nivolumab) Versus Investigator's Choice in Advanced (Unresectable or Metastatic) Melanoma Patients Progressing Post Anti-CTLA-4 Therapy
• Brief Summary: The purpose of the study is to estimate the response rate and compare overall survival of patients taking BMS-936558 to those taking study physician's choice of either Dacarbazine or Carboplatin and Paclitaxel
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unresectable or Metastatic Melanoma

Intervention

• Biological: BMS-936558
• Drug: Dacarbazine
  Other Names:

  • DTIC-Dome
  • DTIC
• Drug: Carboplatin
  Other Names:

  • Paraplatin
  • CBDCA
• Drug: Paclitaxel
  Other Name: Onxol

Study Arms

• Experimental: BMS-936558 3 mg/kg (IV)
  BMS-936558 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
  Intervention: Biological: BMS-936558
• Active Comparator: Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)

  Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

  Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

  Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

  Interventions:

  • Drug: Dacarbazine
  • Drug: Carboplatin
  • Drug: Paclitaxel

Publications *

• Larkin J, Minor D, D'Angelo S, Neyns B, Smylie M, Miller WH Jr, Gutzmer R, Linette G, Chmielowski B, Lao CD, Lorigan P, Grossmann K, Hassel JC, Sznol M, Daud A, Sosman J, Khushalani N, Schadendorf D, Hoeller C, Walker D, Kong G, Horak C, Weber J. Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial. J Clin Oncol. 2018 Feb 1;36(4):383-390. doi: 10.1200/JCO.2016.71.8023. Epub 2017 Jul 3.
• Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH Jr, Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob JJ, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):375-84. doi: 10.1016/S1470-2045(15)70076-8. Epub 2015 Mar 18.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 23, 2022): 405
• Original Estimated Enrollment (submitted: November 2, 2012): 390
• Actual Study Completion Date: December 29, 2020
• Actual Primary Completion Date: February 16, 2016 (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:

• Men & women ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Histologically confirmed Stage III (unresectable)/Stage IV melanoma
• Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Objective evidence of disease progression (clinical or radiological) during or after at least 1 (V600 Wildtype) or at least 2 (V600 mutation positive) prior treatment regimens
• Pre-treatment fresh core, excision or punch tumor biopsy
• Archival Formalin-fixed paraffin-embedded (FFPE) tumor material if available

Exclusion Criteria:

• Any treatment in a BMS-936558 (Nivolumab) trial
• Subjects with condition requiring systemic treatment with either corticosteroids (> 10mg daily prednisone/equivalent) or other immunosuppressive medications within 14 days of study drug administration
• Active, known or suspected autoimmune disease
• Unknown BRAF status
• Active brain metastasis or leptomeningeal metastasis
• Ocular melanoma
• Prior therapy with anti programmed death-1 (anti-PD-1), anti programmed death-ligand 1 (anti-PD-L1) or anti-programmed death-ligand 2 (anti-PD-L2)

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: Austria, Belgium, Brazil, Canada, Denmark, France, Germany, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT01721746
• Other Study ID Numbers: CA209-037; 2012-001828-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: March 2022