Neoadjuvant and Adjuvant Checkpoint Blockade
2 other identifiers
interventional
53
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2016
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 4, 2015
CompletedFirst Posted
Study publicly available on registry
August 10, 2015
CompletedStudy Start
First participant enrolled
February 2, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 26, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 26, 2023
CompletedResults Posted
Study results publicly available
April 5, 2024
CompletedApril 5, 2024
April 1, 2024
7 years
August 4, 2015
November 3, 2023
April 3, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Arm C: Number of Participants With the Pathologic Response Rate
Number of participants with the Pathologic response rate will be assessed by percent viable tumor cells, percent tumor necrosis, presence of fibrosis and melanoma proliferation as assessed by phosphohistone H3 from baseline, to on-treatment and surgical specimens.
up to 2 years
Secondary Outcomes (4)
Arm C: Number of Participants Assessed by Safety and Feasibility of Relatlimab With Nivolumab Delivered in the Neoadjuvant Setting
up to 2 years
Arm C: Number of Participants With Objective Response Rate (ORR) of Relatlimab With Nivolumab Administered in the Neoadjuvant Setting.
Up to 2 years
Arm C: Number of Participants With Recurrence-Free Survival (RFS) and Overall Survival (OS)
up to 12 months
Arm C: Number of Participants With Immunologic and Molecular Mechanisms of Response and Resistance.
up to 2 years
Study Arms (3)
Arm A (nivolumab, surgery)
EXPERIMENTALPatients 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.
Arm B (nivolumab, ipilimumab, surgery)
EXPERIMENTALPatients 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.
Arm C (nivolumab, relatlimab, surgery)
EXPERIMENTALPatients 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.
Interventions
Given IV
Correlative studies
Given IV
Given IV
Undergo surgery
Eligibility Criteria
You may qualify if:
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- Patients must have histologically or cytologically confirmed stage IIIB/C or stage IV oligometastatic melanoma; oligometastatic melanoma is defined as three or fewer areas of resectable disease excluding central nervous system and bone involvement; patients with cutaneous, mucosal, acral, ocular or unknown primary melanomas are eligible for enrollment; for patients with stage IV disease with distant lymph nodes (stage M1a), a maximum of three separate lymph node sites fit the definition of oligometastatic disease; resectable tumors are defined as having no significant vascular, neural or bony involvement; only cases where a complete surgical resection with tumor-free margins can safely be achieved are defined as resectable
- Patients will have at least one melanoma deposit that can undergo serial biopsy (at least 2 time points) during the neoadjuvant phase of the protocol; patients must be willing to provide tumor samples at the time points specified in the Study Procedure Tables
- All patients must undergo a baseline tumor biopsy; in Arms A and B, tumor biopsy for PD-L1 testing (PD-L1 positivity is determined by greater than or equal to 1% of cells staining in the membrane by immunohistochemistry) is required for stratification; PD-L1 status is not required for enrollment on Arm C; the 28-8 clone for PD-L1 testing is required for assessment of PD-L1 status; for patients with stage IV disease, site of tumor biopsy will preferably be from non-lymph node disease site; for PD-L1 testing, the biopsy should contain sufficient tumor content (\> 100 tumor cells/4-micron tissue section); if a sample contains insufficient tumor content, a re-biopsy will be required to obtain a sample with sufficient tumor content prior to treatment
- Patients must be medically fit enough to undergo surgery as determined by the treating medical and surgical oncology team
- Patients who have been previously treated in the adjuvant setting for melanoma will be eligible for treatment after a 28 day wash-out period
- Patients must have measurable disease, defined by RECIST 1.1
- Age \>/= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Absolute neutrophil count (ANC) \>= 1.5 X 10\^9/L (within 28 days of first study treatment)
- Hemoglobin \>= 8.5 g/dL (within 28 days of first study treatment)
- Platelets \>= 100 X 10\^9/L (\>= 60 for hepatocellular carcinoma \[HCC\]) (within 28 days of first study treatment)
- Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 X upper limit of normal (ULN) (within 28 days of first study treatment)
- White blood cells (WBC) \>= 2.0 X 10\^9/L (within 28 days of first study treatment)
- Total bilirubin =\< 1.5 X ULN (except subjects with Gilbert's syndrome who must have normal direct bilirubin) \[3 mg/dL for HCC\] (within 28 days of first study treatment)
- +12 more criteria
You may not qualify if:
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug
- Any major surgery within the last 3 weeks
- Brain metastases, leptomeningeal disease or bone metastases
- Pregnant or lactating female
- Unwillingness or inability to follow the procedures required in the protocol
- Current use of anticoagulants (warfarin, heparin, direct thrombin inhibitors) at therapeutic levels
- Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
- Prior malignancy active within the previous 3 years except for patient's prior diagnosis of melanoma and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast with local control measures (surgery, radiation)
- Subjects with active, known or suspected autoimmune disease; subjects 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
- Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-LAG-3, or anti-CTLA-4 antibody
- Any positive test result for hepatitis B or C virus indicating acute or chronic infection
- Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome
- History of severe hypersensitivity reaction to any monoclonal antibody
- Prisoners or subjects who are involuntarily incarcerated
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (2)
Burton EM, Milton DR, Tetzlaff MT, Wani K, Ross MI, Postow MA, Lazcano R, Glitza IC, Wong MK, Patel SP, Diab A, Gershenwald JE, McQuade JL, Betof Warner A, Prieto VG, Lee JE, Goepfert RP, Fisher SB, Song A, Malke J, Simon JM, Ariyan C, Torres-Cabala CA, Davies MA, Lazar A, Wargo JA, Tawbi HA, Amaria RN. Long-Term Survival and Biomarker Analysis Evaluating Neoadjuvant Plus Adjuvant Relatlimab (anti-LAG3) and Nivolumab (anti-PD1) in Patients With Resectable Melanoma. J Clin Oncol. 2025 Sep 10;43(26):2856-2862. doi: 10.1200/JCO-25-00494. Epub 2025 Jul 10.
PMID: 40638872DERIVEDGorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.
PMID: 36648215DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Rodabe Amaria
- Organization
- M D Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Rodabe N Amaria
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 4, 2015
First Posted
August 10, 2015
Study Start
February 2, 2016
Primary Completion
January 26, 2023
Study Completion
January 26, 2023
Last Updated
April 5, 2024
Results First Posted
April 5, 2024
Record last verified: 2024-04