Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Nivolumab

Dacarbazine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion. Eligible participants may switch to nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.

Participants received dacarbazine, 1000 mg/m\^2, solution administered IV every 3 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion. Eligible participants may cross-over to nivolumab open label treatment, either 3 mg/kg every 2 weeks or 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.

BMS-936558 (Nivolumab)

Placebo matching BMS-936558 (Nivolumab)

Placebo matching Dacarbazine

Bristol-Myers Squibb

The purpose of this study is to compare the clinical benefit, as measured by overall survival, of nivolumab with that of. dacarbazine in patients with previously untreated, unresectable, or metastatic melanoma

Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma

A Phase 3, Randomized, Double-Blind Study of BMS-936558 vs Dacarbazine in Subjects With Previously Untreated, Unresectable or Metastatic Melanoma

OS is defined as the time between the date of randomization and the date of death or the last date the participant was known to be alive.

OS rate is calculated as the percentage of participants alive at the indicated timepoints

Investigator-assessed PFS is defined as the time from randomization to the date of the first documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Patients who died without progressing were considered to have progressed on the date of their death. Those who did not progress or die were documented on the date of their last evaluable tumor assessment. Patients who did not have any on-study tumor assessments and did not die were documented on their date of randomization. Those who started any subsequent anticancer therapy without a prior reported progression were documented on the date of their last evaluable tumor assessment prior to initiation of subsequent anticancer therapy.

The PFS rate at a time point is the estimated percentage of patients who have not progressed and are alive at that time point following randomization and is estimated using the Kaplan-Meier methodology.

ORR is defined as the percentage of participants with a best overall response of Response Evaluation Criteria in Solid Tumors (RECIST) defined complete response (CR) or partial response (PR). RECIST, volume 1.1 for target lesions: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of the longest dimension (LD) of target lesions, taking as reference the baseline sum LD; stable disease=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, and the sum LD must have an absolute increase of ≥5 mm.

Overall Survival is defined as the time between the date of randomization and the date of death or the last date the participant was known to be alive. PD-L1 expression level is defined as the percent of tumor cells demonstrating plasma membrane PD-L1-staining in a minimum of 100 evaluable tumor cells per a Dako PD-L1 IHC (immunohistochemistry) assay (referred to as quantifiable PD-L1 expression). Assessment of OS by PD-L1 expression as measured by a validated assay and comparing OS in patients with tumor PD-L1 expression ≥5% (PD-L1 positive) versus patients with tumor PD-L1 expression \<5% (PD-L1 negative). Tumor tissue samples for PD-L1 testing were collected at screening from metastatic or unresectable sites prior to randomization.

HRQoL is evaluated by mean changes from baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/quality of life composite scale in all randomized patients. The QLQ-30 is a cancer-specific, self-administered questionnaire that contains 30 questions, covering global, functional, and symptom scales. Scores range from 0 to 100. Higher scores on global and functional scales indicate better quality of life (QoL), while higher scores on the symptom scales indicate declining QoL.

All-Cause Mortality = all randomized participants SAEs and NSAEs (Other Adverse Events) = all treated participants

Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion

Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine

Participants received dacarbazine 1000 mg/m\^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion

Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

All participants randomized to receive treatment

An independent data monitoring committee (DMC) found that data from a DMC-requested database lock showed clear survival benefit with nivolumab and thus recommended unblinding the study and switching patients randomized to dacarbazine to nivolumab.

Bristol-Myers Squibb Study Director

Overall Survival (OS)

Progression-free Survival (PFS)

At 6 months

At 12 months

At 18 months

At 24 months

At 36 months

At 48 months

At 60 months

At 72 months

At 84 months

Progression-free Survival (PFS) Rate

Objective Response Rate (ORR)

PD-L1 positive participants (cutoff=5%)

PD-L1 negative/indeterminate participants (cutoff=5%)

Overall Survival by Programmed Cell Death Ligand 1 (PD-L1) Expression Level

Overall Survival (OS) Rate

Week 7

Week 13

Week 19

Week 25

Week 31

Week 37

Week 43

Week 49

Week 55

Week 61

Week 67

Week 73

Week 79

Week 85

Week 91

Week 97

Week 103

Week 109

Week 115

Week 121

Week 127

Week 133

Week 139

Week 145

Week 151

Week 157

Week 163

Week 169

Week 175

Week 181

Week 187

Week 193

Week 199

Week 205

Week 211

Week 217

Week 223

Week 229

Week 235

Week 241

Week 247

Week 253

Week 259

Week 265

Week 271

Week 277

Week 283

Week 289

Week 295

Week 301

Week 307

Week 313

Week 319

Week 325

Week 331

Week 337

Week 343

Week 349

Week 355

Week 361

Week 367

Week 373

Week 379

Week 385

Week 391

Week 397

Week 403

All randomized participants with available measurements

Change From Baseline in Health-related Quality of Life (HRQoL) Scores

OS is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive. OS data for this endpoint was collected after the primary completion date up until study completion.

Overall Survival (OS) Extended

6 months

12 months

18 months

24 months

36 months

48 months

60 months

72 months

84 months

OS rate is calculated as the percentage of participants alive at the indicated timepoints. Data for this endpoint was collected after the primary completion date up until study completion. The OS rate for the 6 month and 12 month timepoints reflect updated data that was collected after the primary completion date.

Overall Survival (OS) Rate Extended

Pre-Treatment

Treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma	NCT01721772	Melanoma	BMS-936558 (Niv... Placebo matchin... Dacarbazine Placebo matchin...	18 Years -	Bristol-Myers Squibb
Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma	NCT01721772	Melanoma	BMS-936558 (Niv... Placebo matchin... Dacarbazine Placebo matchin...	18 Years -	Bristol-Myers Squibb
Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma	NCT01721772	Melanoma	BMS-936558 (Niv... Placebo matchin... Dacarbazine Placebo matchin...	18 Years -	Bristol-Myers Squibb
Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma	NCT01721772	Melanoma	BMS-936558 (Niv... Placebo matchin... Dacarbazine Placebo matchin...	18 Years -	Bristol-Myers Squibb

Spots Global Cancer Trial Database for placebo matching dacarbazine