A Phase I Trial of a Vaccine Combining Multiple Class I Peptides and Montanide ISA 51VG With Escalating Doses of Anti-PD-1 Antibody Nivolumab or Ipilimumab With Nivolumab For Patients With Resected Stages IIIC/ IV Melanoma

H. Lee Moffitt Cancer Center and Research Institute1 site in 1 country73 target enrollmentAugust 13, 2010

ConditionsMelanoma (Skin)

InterventionsNY-ESO-1 157-165 (165V)Nivolumab Montanide ISA 51 vegetable grade (VG)Apheresis Procedure Ipilimumab

DrugsNivolumab Montanide ISA 51 vegetable grade (VG)Ipilimumab

Overview

Phase: Phase 1
Intervention: NY-ESO-1 157-165 (165V)
Conditions: Melanoma (Skin)
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Enrollment: 73
Locations: 1
Primary Endpoint: Time to Relapse
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to test the side effects of an investigational vaccine with an immune booster, or 2 different boosters together. Investigators also want to find out its effects on the immune system and whether it will decrease the chance that melanoma will return.

Detailed Description

Up to 5 dose cohorts will be studied. Participants will be assigned to a dose cohort in the order they enter the study. * 1 mg/kg of NIVOLUMAB + peptide vaccine (1 mg/kg cohort), then * 3 mg/kg of NIVOLUMAB + peptide vaccine (3 mg/kg cohort), then * 10 mg/kg of NIVOLUMAB + peptide vaccine (10 mg/kg cohort), then * 1 mg/kg NIVOLUMAB + ipilimumab 3 mg/kg combination cohort * 3 mg/kg NIVOLUMAB + ipilimumab 1 mg/kg combination cohort

Registry

clinicaltrials.gov

Start Date

August 13, 2010

End Date

January 6, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologic diagnosis of resected Stages IIIC/ IV melanoma, with no evidence of disease clinically and radiologically. All melanomas regardless of primary site of disease will be allowed.
•HLA-A\*0201 positive as determined by deoxyribonucleic (DNA) allele-specific polymerase chain reaction (PCR) assay; HLA restriction is not required for cohort 4
•Positive staining of most recently resected tumor tissue with antibodies to 1 or more of the following: human melanoma black 45 (HMB 45) for gp100, NY-ESO-1, and/or MART-1
•Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
•Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events have either returned to baseline or stabilized.
•Prior treated brain or meningeal metastases must be without magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids (\> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
•Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks before study drug administration. No radiopharmaceuticals (strontium, samarium) within 8 weeks before study drug administration.
•Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration.
•Completed nitrosourea treatment at least 6 weeks before administration of any study drug.
•Prior surgery that required general anesthesia must be completed at least 4 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and participants should be recovered.

Exclusion Criteria

•History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
•Systemic hypersensitivity to Montanide ISA 51 VG or any vaccine component.
•Prior non-melanoma malignancy active within the previous 2 years except for 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.
•Any active autoimmune disease or documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for participants with vitiligo or resolved childhood asthma/atopy.
•Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
•Positive tests for hepatitis B virus surface antigen (HBV SAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
•Prior therapy with an anti-Programmed Death-1(anti-PD-1), anti-Programmed Death-Ligand 1 (anti-PD-L1), anti-programmed death-ligand-2 (anti-PD-L2), or anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody(or any other antibody targeting T cell co-stimulation pathways).
•Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids.
•Underlying medical condition (eg, a condition associated with diarrhea) that, in the Investigator's opinion, would make the administration of either study drug or both study drugs hazardous to the participant or obscure the interpretation of toxicity determination or adverse events.
•Pregnant or nursing.

Arms & Interventions

Nivolumab and Peptide Vaccine

Cohorts 1 through 3: Participants will receive nivolumab with the peptide vaccine within 8 days after their first apheresis procedure. Vaccine Combining Multiple Class I Peptides and Montanide ISA 51 VG with Escalating Doses of Anti-PD-1 Antibody Nivolumab (BMS-936558). Level 1: 1 mg/kg Nivolumab + peptide vaccine. Level 2: 3 mg/kg Nivolumab + peptide vaccine. Level 3: 10 mg/kg Nivolumab + peptide vaccine.

Intervention: NY-ESO-1 157-165 (165V)

Nivolumab and Peptide Vaccine

Intervention: Nivolumab

Nivolumab and Peptide Vaccine

Intervention: Montanide ISA 51 vegetable grade (VG)

Nivolumab and Peptide Vaccine

Intervention: Apheresis Procedure

Nivolumab and Ipilimumab

Cohorts 4 and 5. Participants will receive their first dose of nivolumab with ipilimumab within 28 days after screening blood draws. Both drugs will be given. Cohort 4: nivolumab 1mg/kg plus ipilimumab 3mg/kg. Cohort 5: nivolumab 3mg/kg plus ipilimumab 1mg/kg.

Intervention: Nivolumab