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This is the Investigator Sponsored Trial (IST) clinical trial protocol for the Phase II in neoadjuvant melanoma discussed by Principal Investigator Dr. Amaria at MD Anderson (Nivo/Opdivo + Relatlimab is Arm C). Note during the BMY ASCO2021 presentation, a Phase III trial in Adjuvant Melanoma was one of the future planned expansion opportunities for Relatlimab.
Neoadjuvant and Adjuvant Checkpoint Blockade
ClinicalTrials.gov Identifier: NCT02519322
Recruitment Status : Active, not recruiting
First Posted : August 10, 2015
Last Update Posted : August 27, 2021
Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
Study Description
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Brief Summary:
This randomized phase II trial studies how well nivolumab with or without ipilimumab or relatlimab before surgery works in treating patients with stage IIIB-IV melanoma that can be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, and relatlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab alone or in combination with ipilimumab or relatlimab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Condition or disease
Intervention/treatment
Phase
Cutaneous MelanomaMucosal MelanomaOcular MelanomaStage III Acral Lentiginous Melanoma AJCC v7Stage IIIB Cutaneous Melanoma AJCC v7Stage IIIB Uveal Melanoma AJCC v7Stage IIIC Cutaneous Melanoma AJCC v7Stage IIIC Uveal Melanoma AJCC v7Stage IV Acral Lentiginous Melanoma AJCC v6 and v7Stage IV Cutaneous Melanoma AJCC v6 and v7Stage IV Uveal Melanoma AJCC v7
Biological: IpilimumabOther: Laboratory Biomarker AnalysisBiological: NivolumabBiological: RelatlimabProcedure: Therapeutic Conventional Surgery
Study Design
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Study Type :
Interventional (Clinical Trial)
Estimated Enrollment :
53 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Neoadjuvant and Adjuvant Checkpoint Blockade in Patients With Clinical Stage III or Oligometastatic Stage IV Melanoma
Actual Study Start Date :
February 2, 2016
Estimated Primary Completion Date :
December 1, 2022
Estimated Study Completion Date :
December 1, 2022
Arms and Interventions
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Arm
Intervention/treatment
Experimental: Arm A (nivolumab, surgery)
Patients receive nivolumab IV over 30 minutes on days 1, 15, 29, and 43. Patients then undergo surgery on day 57. After surgery, patients receive nivolumab IV over 30 minutes every 2 weeks for 13 doses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
BMS-936558
MDX-1106
NIVO
ONO-4538
Opdivo
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Experimental: Arm B (nivolumab, ipilimumab, surgery)
Patients receive nivolumab IV over 1 hour and ipilimumab IV over 90 minutes on days 1, 22, and 43. Patients then undergo surgery on day 57. After surgery, patients receive nivolumab IV over 30 minutes every 2 weeks for 13 doses in the absence of disease progression or unacceptable toxicity.
Experimental: Arm C (nivolumab, relatlimab, surgery)
Patients receive nivolumab IV over 1 hour and relatlimab IV over 1 hour on days 1 and 29. Patients then undergo surgery on day 57. After surgery, patients receive nivolumab IV over 1 hour and relatlimab IV over 1 hour every 4 weeks for 10 doses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Nivolumab
Given IV
Other Names:
BMS-936558
MDX-1106
NIVO
ONO-4538
Opdivo
Biological: Relatlimab
Given IV
Other Names:
BMS-986016
BMS986016
Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Outcome Measures
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Primary Outcome Measures :
Proportion of patients experiencing pathologic response to neoadjuvant nivolumab monotherapy [ Time Frame: Up to 2 years ]
The proportion of patients experiencing pathologic response will be computed with associated 95% confidence interval for each treatment arm.
Proportion of patients experiencing pathologic response to neoadjuvant nivolumab and ipilimumab combination therapy [ Time Frame: Up to 2 years ]
The proportion of patients experiencing pathologic response will be computed with associated 95% confidence interval for each treatment arm.
Secondary Outcome Measures :
Immunological response, assessed by change in T cell infiltrate [ Time Frame: Baseline up to 2 years ]
Immunologic response will be assessed by change in T cell infiltrate from baseline to each study procedure visit (approximately 9 weeks). The change in T cell infiltrate will be assessed over time for each treatment arm using a generalized linear mixed model with terms for visit, stage of disease, and PD-L1 tumor status.
Proportion of patients experiencing objective response (complete response, partial response, stable disease, and progressive disease) [ Time Frame: Up to 2 years ]
The proportion of patients experiencing objective response will be computed with associated 95% confidence interval for each treatment arm.
Recurrence-free survival [ Time Frame: Time of surgical resection to the date of documented disease recurrence, assessed up to 2 years ]
Recurrence-free survival will be estimated using the Kaplan-Meier method for each treatment arm.
Overall survival [ Time Frame: From treatment start date to date of death, assessed up to 2 years ]
Overall survival will be estimated using the Kaplan-Meier method for each treatment arm.
Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ]
Safety and tolerability will be assessed by vital signs, laboratory assessments, adverse events, and serious adverse events for the safety population. Categorical measures will be summarized using frequencies and percentages while continuous variables will be summarized using mean, standard deviation, median, minimum, and maximum.
Other Outcome Measures:
Molecular markers with potential predictive value for the treatment of melanoma [ Time Frame: Up to 2 years ]
Various molecular markers with potential predictive value for the treatment of melanoma may be assessed. The association between change in tumor size and immune infiltration within each treatment arm will be assessed using a generalized linear mixed model where change in tumor size will be the dependent variable and gene expression, visit, and gene expression-by-visit interaction will be the independent variables. The association between RFS and immune infiltration within each treatment arm will be determined by a Cox proportional hazards regression model.