Phase I/Phase II Open Label Study of the TLR3 Agonist Poly-ICLC as an Adjuvant for NY-ESO-1 Protein Vaccination With or Without Montanide ® ISA-51 VG in Patients With High Risk Melanoma in Complete Clinical Remission
This is a Phase I open label dose escalation study of the TLR3 agonist Poly-ICLC as an
adjuvant for NY-ESO-1 protein vaccination in patients with high risk melanoma in clinical
complete remission (cCr), followed by a randomized Phase II component in which patients will
be randomized to subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD
(Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide® ISA-51 VG (Montanide)
Patients with histological confirmed malignant melanoma, AJCC Stages: IIB, IIC, III or IV,
who are in complete clinical remission (cCr) but at high risk of disease recurrence, will be
eligible for enrollment, regardless of whether antigen expression in the autologous tumor
can be demonstrated by either PCR or immunohistochemistry.
- Phase I: To define the safety of subcutaneous vaccination with NY-ESO-1 protein,
Montanide and escalating doses of Poly-ICLC.
- Phase II: To evaluate the induction of humoral and T cell (CD4+ and CD8+) immunity to
subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given
with or without Montanide.
- Evaluation of primary tumor expression of NY-ESO-1 by IHC or RT-PCR.
- Histologic quantitation of original tumor TILs (tumor infiltrating lymphocytes), CD3+
cells, evaluation of mitotic index and correlation of this data with immunologic
- Correlation of NY-ESO-1 specific T cell responses with HLA type
- Investigation of polymorphisms for TLR3 through germline SNP analysis.
- Clinical Outcome (Time to Progression) reported descriptively.
- Skin section analysis of protein/adjuvant treated sites for immune cell infiltration
and gene expression analysis
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I, to define the safety of subcutaneous vaccination with NY-ESO-1 protein, Montanide and escalating doses of Poly-ICLC
Up to 3 cohorts of 3 patients will be given a subcutaneous vaccination of 100µg NY-ESO-1 protein emulsified in 1.1mL Montanide® ISA-51VG (day 1) with escalating doses of Poly-ICLC. Dose-escalation will continue if no DLTs are observed in the 3 patients in a given cohort.
Disease status is assessed at baseline, wks 4 & 12 and after 4th vaccination (wks 14 & 22). At wk 52, disease status is assessed through patient follow-up with study physicians or through contact with the patient's regular treating physician.
Nina Bhardwaj, MD, PhD
New York University Langone Medical Center
United States: Food and Drug Administration
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