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

Study Overview
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Brief Summary
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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.

Official Title
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Clinical Trial of Nivolumab (BMS-936558) Combined With Ipilimumab Followed by Nivolumab Monotherapy as First-Line Therapy of Subjects With Histologically Confirmed Stage III (Unresectable) or Stage IV Melanoma CheckMate 401: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 401

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination therapy: Nivolumab + Ipilimumab<br>Nivolumab + Ipilimumab specified dose on specified days | Drug: Nivolumab<br> <br> Drug: Ipilimumab<br> <br> |
| Experimental: Monotherapy: Nivolumab<br>Nivolumab specified dose on specified days | Drug: Nivolumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Participants With High-Grade (CTCAE v4.0 Grade 3-5) Treatment-Related Select Adverse Events | 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 | From first dose to 30 days after last dose (up to approximately 37 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Participants With All High-Grade (Grades 3-5) Select Adverse Events | Incidence of participants with high-grade (grade 3-5) select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, infusion-related, or hypersensitivity | 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 | Median time to onset (grades 3-4) of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity | 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 | Median time to resolution (Grades 3-4) of select adverse events including pulmonary, gastrointestinal, skin, renal, hepatic, endocrine, infusion-related, or hypersensitivity | From first dose to 30 days after last dose (up to approximately 37 months) | 
| Time to Resolution of an Adverse Event (AE) | 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 | From first dose to 30 days after last dose (up to approximately 37 months) | 
| Overall Survival (OS) | 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 | Up to approximately 37 months | 
| Incidence of Participants With Adverse Events | 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 | From first dose to 30 days after last dose (up to approximately 37 months) | 
| Incidence of Participants With Select Adverse Events | 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 | From first dose to 30 days after last dose (up to approximately 37 months) | 
| Incidence of Participants With Laboratory Abnormalities - Liver | 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) | From first dose to 30 days after last dose (up to approximately 37 months) | 
| Incidence of Participants With Laboratory Abnormalities - Thyroid | 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) | From first dose to 30 days after last dose (up to approximately 37 months) | 
| Objective Response Rate (ORR) | 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 | Up to approximately 37 months | 
| Progression Free Survival (PFS) | 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. | Up to approximately 37 months |