Nivolumab Combined With Ipilimumab Followed by Nivolumab Monotherapy as First-Line Treatment for Patients With Advanced Melanoma

Phase 3

Completed

Conditions: Melanoma

Interventions: Drug: Nivolumab
Drug: Ipilimumab

Registration Number: NCT02599402

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The purpose of this study is to determine the effects of combination treatment of Nivolumab with Ipilimumab followed by Nivolumab monotherapy in patients with previously untreated advanced Melanoma.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 533

Inclusion Criteria

Potential subjects must have advanced Melanoma (stage III or IV as confirmed by biopsy) with spread to other sites in the body and unable to be removed by surgery.
Potential subjects must be newly diagnosed with advanced melanoma and received no treatment for the advanced disease.

NOTE: Prior adjuvant or neoadjuvant melanoma therapy (including anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways, such as anti-CD-137) is permitted if the therapy was used in the adjuvant or neoadjuvant setting but not in the metastatic setting. These drugs must be discontinued 6 months prior to study entry and the side effects related to the prior therapy resolved.

Potential subjects (with disease spread to brain) who previously received primary treatment are permitted if there was no evidence of disease as confirmed by the MRI (at least 2 weeks after the primary treatment is complete and with in 6 weeks of the first dose of the study drug). Potential subjects must not have received intravenous steroid treatment (>10 mg/day) intravenously for at least 2 weeks prior to study drug administration.

Exclusion Criteria

Leptomenigeal metastases
Subjects with autoimmune disease. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
All side effects from previous primary treatments other than alopecia, fatigue, or peripheral neuropathy must have resolved to Grade 1 or baseline before administration of study drug.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combination therapy: Nivolumab + Ipilimumab	Ipilimumab	Nivolumab + Ipilimumab specified dose on specified days
Combination therapy: Nivolumab + Ipilimumab	Nivolumab	Nivolumab + Ipilimumab specified dose on specified days
Monotherapy: Nivolumab	Nivolumab	Nivolumab specified dose on specified days

Primary Outcome Measures

Name	Time	Method
Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events	From first dose to 30 days after last dose (up to approximately 37 months)	Incidence of participants with high-grade (CTCAE v4.0 grade 3-5) treatment-related, select adverse events of potentially immune-mediated etiology including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity

Secondary Outcome Measures

Name	Time	Method
Median Time to Resolution (Grades 3-4) of Select Adverse Events	From first dose to 30 days after last dose (up to approximately 37 months)	Median time to resolution (Grades 3-4) of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity
Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events	From first dose to 30 days after last dose (up to approximately 37 months)	Incidence of participants with high-grade (grade 3-5) select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, infusion-related, or hypersensitivity
Median Time to Onset (Grades 3-4) of Select Adverse Events	From first dose to 30 days after last dose (up to approximately 37 months)	Median time to onset (grades 3-4) of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity
Time to Resolution of an Adverse Event (AE)	From first dose to 30 days after last dose (up to approximately 37 months)	Resolution of an adverse event (AE) is defined as a participant experiencing complete resolution or improvement to the baseline of any grade AE including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity
Overall Survival (OS)	Up to approximately 37 months	Overall survival is defined from the time of first dosing date to the date of death. A participant who has not died will be censored at the last known date alive
Incidence of Participants With Adverse Events	From first dose to 30 days after last dose (up to approximately 37 months)	The assessment of safety is measured by the incidence of participants who experienced any grade of adverse events (AEs), treatment-related AEs, serious adverse events (SAEs), and deaths
Incidence of Participants With Select Adverse Events	From first dose to 30 days after last dose (up to approximately 37 months)	The assessment of safety is measured by the incidence of participants who experienced any grade of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity
Incidence of Participants With Laboratory Abnormalities - Liver	From first dose to 30 days after last dose (up to approximately 37 months)	Safety assessment is measured by the incidence of participants who experienced a liver laboratory abnormality in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Upper Limit of Normal (ULN)
Incidence of Participants With Laboratory Abnormalities - Thyroid	From first dose to 30 days after last dose (up to approximately 37 months)	Safety assessment is measured by the incidence of participants who experienced a thyroid laboratory abnormality in Free T3 (FT3), Free T4 (FT4), Lower Limit of Normal (LLN)
Objective Response Rate (ORR)	Up to approximately 37 months	Objective response rate is defined as the percentage of participants with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of all treated participants
Progression Free Survival (PFS)	Up to approximately 37 months	Progression free survival per investigator assessment is defined as radiological evidence of progression, significant clinical symptomatic progression, or the need to introduce a non-study drug therapy.