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NCT01721746

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)

Completed Phase 3 Results posted Last updated 19 April 2022
What this trial tests

Phase 3 trial testing BMS-936558 in Unresectable or Metastatic Melanoma in 405 participants. Completed in 29 December 2020.

Timeline
21 December 2012
Primary endpoint
16 February 2016
29 December 2020

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment405
Start date21 December 2012
Primary completion16 February 2016
Estimated completion29 December 2020
Sites95 locations across Denmark, France, Italy, Netherlands, Belgium, Austria, United Kingdom, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Unresectable or Metastatic Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Primary · 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

GroupValue95% CI
Nivolumab27.222.0 – 32.9
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)9.85.3 – 16.1
Overall Survival (OS) Primary · 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.

GroupValue95% CI
Nivolumab15.7412.88 – 19.88
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)14.3911.66 – 18.17
Progression Free Survival (PFS) Secondary · 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.

GroupValue95% CI
Nivolumab3.122.33 – 3.52
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)3.652.30 – 5.29
Objective Response Rate (ORR) by Baseline PD-L1 Expression Secondary · 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.

<5% PD-L1 expression
GroupValue95% CI
Nivolumab15.39.7 – 22.5
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)13.86.1 – 25.4
>=5% PD-L1 expression
GroupValue95% CI
Nivolumab43.233.9 – 53.0
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)12.24.1 – 26.2
Overall Survival (OS) by PD-L1 Positive Secondary · 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.

GroupValue95% CI
Nivolumab31.4420.57 – 46.69
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)16.7211.83 – 31.44
Overall Survival (OS) by PD-L1 Negative Secondary · 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.

GroupValue95% CI
Nivolumab11.147.72 – 13.21
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)11.768.05 – 17.81
Mean Change From Baseline in Health-related Quality of Life (HRQoL) Secondary · 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

Physical Functioning Follow-Up 1
GroupValue95% CI
Nivolumab-7.97± 20.49
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)-12.73± 21.47
Physical Functioning Follow-Up 2
GroupValue95% CI
Nivolumab-3.66± 16.05
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)-7.14± 16.02
Role Functioning Follow-Up 1
GroupValue95% CI
Nivolumab-14.94± 31.13
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)-15.91± 29.76
Role Functioning Follow-Up 2
GroupValue95% CI
Nivolumab-7.80± 25.56
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)-8.33± 21.52
Emotional Functioning Follow-Up 1
GroupValue95% CI
Nivolumab-5.09± 21.59
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)-15.48± 24.48
Emotional Functioning Follow-Up 2
GroupValue95% CI
Nivolumab-0.94± 19.15
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)-5.36± 25.98
Cognitive Functioning Follow-Up 1
GroupValue95% CI
Nivolumab-7.58± 16.79
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)-7.94± 17.17
Cognitive Functioning Follow-Up 2
GroupValue95% CI
Nivolumab-3.49± 15.43
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)-1.19± 13.55

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose to 100 days post last dose (Up to 96 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nivolumab
Serious: 191/268 (71%)
Deaths: 206/268
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)
Serious: 37/102 (36%)
Deaths: 88/102

Serious adverse events (193 terms)

ReactionSystemNivolumabInvestigator's Choice (Dac…
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumoniaInfections and infestations
Metastatic malignant melanomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Back painMusculoskeletal and connective tissue disorders
General physical health deteriorationGeneral disorders
Abdominal painGastrointestinal disorders
PyrexiaGeneral disorders
DehydrationMetabolism and nutrition disorders
Malignant melanomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DyspnoeaRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
DiarrhoeaGastrointestinal disorders
SepsisInfections and infestations
OsteoarthritisMusculoskeletal and connective tissue disorders
Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Cardiac arrestCardiac disorders
NauseaGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
Urinary tract infectionInfections and infestations
HyperglycaemiaMetabolism and nutrition disorders
Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemorrhage intracranialNervous system disorders
Confusional statePsychiatric disorders
HypotensionVascular disorders
Other adverse events (61 terms — click to expand)

ReactionSystemNivolumabInvestigator's Choice (Dac…
FatigueGeneral disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
Back painMusculoskeletal and connective tissue disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
HeadacheNervous system disorders
Oedema peripheralGeneral disorders
Aspartate aminotransferase increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
AstheniaGeneral disorders
InsomniaPsychiatric disorders
MyalgiaMusculoskeletal and connective tissue disorders
VitiligoSkin and subcutaneous tissue disorders
DizzinessNervous system disorders
AlopeciaSkin and subcutaneous tissue disorders
Alanine aminotransferase increasedInvestigations
HypothyroidismEndocrine disorders
PainGeneral disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Weight decreasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
Urinary tract infectionInfections and infestations
Dry skinSkin and subcutaneous tissue disorders
Blood alkaline phosphatase increasedInvestigations
Rash maculo-papularSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
DyspepsiaGastrointestinal disorders
HypertensionVascular disorders

Most-reported serious reactions: Malignant neoplasm progression, Pneumonia, Metastatic malignant melanoma, Back pain, General physical health deterioration, Abdominal pain, Pyrexia, Dehydration.

Data from ClinicalTrials.gov NCT01721746 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. 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.
    Weber JS, D'Angelo SP, Minor D, Hodi FS, et al · · 2015 · cited 2037× · PMID 25795410 · DOI 10.1016/s1470-2045(15)70076-8
  2. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.
    Topalian SL, Sznol M, McDermott DF, Kluger HM, et al · · 2014 · cited 1751× · PMID 24590637 · DOI 10.1200/jco.2013.53.0105
  3. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  4. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade.
    Morad G, Helmink BA, Sharma P, Wargo JA. · · 2021 · cited 1197× · PMID 34624224 · DOI 10.1016/j.cell.2021.09.020
  5. New horizons in tumor microenvironment biology: challenges and opportunities.
    Chen F, Zhuang X, Lin L, Yu P, et al · · 2015 · cited 521× · PMID 25857315 · DOI 10.1186/s12916-015-0278-7
  6. The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma.
    Mahoney KM, Freeman GJ, McDermott DF. · · 2015 · cited 440× · PMID 25823918 · DOI 10.1016/j.clinthera.2015.02.018
  7. Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis.
    D'Angelo SP, Larkin J, Sosman JA, Lebbé C, et al · · 2017 · cited 439× · PMID 28056206 · DOI 10.1200/jco.2016.67.9258
  8. 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.
    Larkin J, Minor D, D'Angelo S, Neyns B, et al · · 2018 · cited 377× · PMID 28671856 · DOI 10.1200/jco.2016.71.8023

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