VX15/2503 with or without Ipilimumab and/or Nivolumab in Treating Patients with Resectable Stage IIIB-D Melanoma
18 Years and older, Male and Female
Winship4400-18 (primary)
NCI-2018-01229
IRB00104273
Summary
This phase I trial studies how well VX15/2503 (pepinemab) with or without ipilimumab and/or nivolumab works in treating patients with stage IIIB-D melanoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as VX15/2503, ipilimumab, and nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Objectives
PRIMARY OBJECTIVE:
I. Evaluate the effect of VX15/2503 in combination with immune checkpoint inhibitors on T cell infiltrate into the tumor microenvironment in involved and uninvolved lymph nodes and peripheral blood.
SECONDARY OBJECTIVES:
I. Evaluate the effect of VX15/2503 in combination with immune checkpoint inhibitors on the immune profile of involved and uninvolved lymph nodes and peripheral blood.
II. Assess safety and tolerability of profile and tolerability of single agent VX15/2503 to the combination of VX15/2503 and immune checkpoint inhibitors in patients with resectable metastatic melanoma.
III. Document pathologic response rates of VX15/2503 and immune checkpoint inhibitors in patients with resectable melanoma.
IV. Compare pathologic response to radiographic response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients receiving single agent VX15/2503 and combination VX12/2503 and immune checkpoint inhibitors in patients with resectable melanoma.
OUTLINE: Patients are assigned to 1 of 5 arms.
ARM I: Patients receive pepinemab intravenously (IV) over 60 minutes and nivolumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.
ARM II: Patients receive pepinemab IV over 60 minutes and ipilimumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.
ARM III: Patients receive pepinemab IV over 60 minutes, nivolumab IV over 30 minutes, and ipilimumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.
ARM IV: Patients receive nivolumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.
ARM V: Patients undergo surgery.
After completion of study treatment, patients are followed up at 90 days, every 12 weeks for 2 years, every 6 months for 3 years, then annually up to 10 years.
Eligibility
- Must be at least >= 18 years of age.
- Stage IIIB, IIIC, IIID histologically-proven melanoma.
* Cancer confirmed to be surgically resectable, with surgery evaluation with planned prior to resection.
* No prior immunotherapy with CTLA-4, anti PD-1 or VX15/2503. Prior interferon (at least 1 year prior to consent) will be allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Absolute neutrophil count >= 1,500 cells/uL.
- Platelets >= 100,000/uL.
- Hemoglobin >= 9.0g/dL (may receive packed red blood cells [PRBC] transfusion).
- Total bilirubin =< 1.5 x the upper limit of normal (ULN).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN.
- Albumin >= 3.0 g/dL.
- Serum creatinine =< 1.5 x ULN OR calculated creatinine clearance of >= 50 mL/min using Cockcroft-Gault formula.
- International normalized ration (INR) =< 1.5. Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level < 1.1 U/mL are allowed on the trial.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- Ability to understand and willingness to sign a written informed consent document.
- Female subjects of childbearing potential must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study treatment and 5 months after last dose of study treatment.
- Male subjects must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study treatment and 7 months after last dose of study treatment.
- Female subjects of childbearing age must have a negative serum pregnancy test at study entry.
- Patients in cohort E may proceed directly to surgery without meeting the eligibility criteria above assuming they are deemed candidates and undergo appropriate testing for the planned operation
Treatment Sites in Georgia
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