Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma

Phase 2

Completed

• Conditions: Metastatic Melanoma; Unresectable Melanoma
• Interventions: Drug: Nivolumab; Drug: Ipilimumab; Drug: Placebo

• Registration Number: NCT01927419
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

The primary purpose of this study is to compare the objective response rate, as determined by investigators, of Nivolumab combined with Ipilimumab versus Ipilimumab monotherapy in patients with untreated, unresectable, or metastatic melanoma

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-08-20
• Study First Submitted QC: 2013-08-20
• Study First Posted: 2013-08-22
• Study Start: 2013-08-23
• Primary Completion: 2014-07-24
• Disposition First Submitted: 2015-07-03
• Disposition First Submitted QC: 2015-07-17
• Disposition First Posted: 2015-08-07
• Results First Submitted: 2015-11-03
• Results First Submitted QC: 2016-01-08
• Results First Posted: 2016-02-08
• Study Completion: 2021-02-26
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-16
• Last Update Posted: 2022-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 142

Inclusion Criteria

• Eastern Cooperative Oncology Group performance status of 0 or 1
• Histologically confirmed unresectable Stage III or Stage IV melanoma
• No prior systemic anticancer therapy for unresectable or metastatic melanoma. Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized
• Tumor tissue obtained in the metastatic setting or from an unresectable site must be provided for biomarker analyses and sent to the central laboratory. Biopsy should be excisional, incisional punch, or core needle. Fine needle aspirates or other cytology samples are insufficient
• Known BRAF V600 mutation status as determined by an FDA-approved test. Patients with either V600 wild-type or V600 mutation-positive melanoma are eligible.

Key

Exclusion Criteria

• Active brain metastases or leptomeningeal metastases. Patients with treated brain metastases are eligible if there is no evidence of progression on magnetic resonance imaging scan for at least 8 weeks after completion of treatment and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
• Ocular melanoma
• Patients with active, known, or suspected autoimmune disease. Those with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nivolumab + Ipilimumab	Ipilimumab	Participants received (Part 1) 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
Placebo + Ipilimumab	Placebo	Participants received (Part 1) placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
Placebo + Ipilimumab	Ipilimumab	Participants received (Part 1) placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
Nivolumab + Ipilimumab	Nivolumab	Participants received (Part 1) 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) - BRAF Wild-type (WT) Participants	From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)	Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria.; CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (\<10 mm).; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) - BRAF Mutant Participants	From randomization to progression or death (up to approximately 88 months)	PFS is defined as the time between the date of randomization and the first date of documented progression, as assessed by the investigator, 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 died were censored on the date of their last evaluable tumor assessment.; PFS values are based on Kaplan-Meier Estimates.
Progression-Free Survival (PFS) - BRAF Wild-type (WT) Participants	From randomization to progression or death (up to approximately 88 months)	PFS is defined as the time between the date of randomization and the first date of documented progression, as assessed by the investigator, 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 died were censored on the date of their last evaluable tumor assessment.; PFS values are based on Kaplan-Meier Estimates.
Objective Response Rate (ORR) - BRAF Mutant Participants	From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)	Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria.; CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (\<10 mm).; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Overall Quality of Life (QOL) C30 Score	From Baseline (prior to start of study treatment) to Week 25 after first dose	The EORTC QLQ-C30 version 3 is a questionnaire developed to assess the QOL of cancer patients. The questionnaire is a 30-item tool, and it comprises 6 functional subscales (physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as 9 symptom subscales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).; Scores for each subscale range from 0 to 100. For the 6 functional subscales, a higher score represents a better level of functioning/health status. For the 9 symptom subscales, a lower score represents a better outcome (low level of symptomatology).; Scores for the 15 subscales are presented individually.

Trial Locations

Locations (21)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Dartmouth-Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

San Francisco Oncology Associates; 🇺🇸 San Francisco, California, United States

University Of Louisville Medical Center, Inc., Dba; 🇺🇸 Louisville, Kentucky, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

NYU Clinical Cancer Center; 🇺🇸 New York, New York, United States

University Of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

Memorial Sloan Kettering Nassau; 🇺🇸 New York, New York, United States

The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

GHS Cancer Institute; 🇺🇸 Greenville, South Carolina, United States

Hopital Larrey; 🇫🇷 Toulouse, France

Comprehensive Cancer Centers Of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Washington University School Of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

Orlando Health Inc; 🇺🇸 Orlando, Florida, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

St. Luke's Hospital; 🇺🇸 Easton, Pennsylvania, United States

University Of Wisconsin Paul P Carbone Comprehensive Ca Ctr; 🇺🇸 Madison, Wisconsin, United States