Phase I/II study of resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with melanoma.

Media type: E-Article

Title: Phase I/II study of resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with melanoma

Contributor: Sabado, Rachel Lubong; Pavlick, Anna C.; Gnjatic, Sacha; Cruz, Crystal M; Vengco, Isabelita; Hasan, Farah; Darvishian, Farbod; Chiriboga, Luis; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Adams, Sylvia; Ott, Patrick Alexander; Jungbluth, Achim A; Pan, Linda S.; Venhaus, Ralph Rudolph; Bhardwaj, Nina

imprint: American Society of Clinical Oncology (ASCO), 2012

Language: English

DOI: 10.1200/jco.2012.30.15_suppl.2589

ISSN: 0732-183X; 1527-7755

Origination:

Footnote:

Description: 2589 Background: The TLR 7/8 agonist, Resiquimod has been shown to induce local activation of immune cells, production of cytokines, and antigen-presentation by dendritic cells, features desirable for cancer vaccine adjuvants. In this study, we evaluated the safety and immunogenicity of vaccination with NY-ESO-1 protein emulsified in Montanide ISA-51 VG when given with or without Resiquimod in patients with surgically resected stage IIB-IV melanoma patients. Methods: This is a two-part study design. Part I represents an open-label dose-escalation with Resiquimod using 2 cohorts treated with 100ug NY-ESO-1 protein emulsified in 1.25mL Montanide (day1) followed by topical application of 1000mg of the 0.2% Resiquimod gel on days 1 and 3 for cohort-1 (N=3) or days 1, 3, and 5 for cohort-2 (N=3). The cycles were repeated every 3 weeks, total of 4 cycles. Part II of the study is blinded. Patients were randomized to receive 100ug NY-ESO-1 protein emulsified in 1.25mL Montanide (day1) followed by topical application of placebo gel (Arm-A; N=8) or 1000mg of 0.2% Resiquimod gel (Arm-B; N=12) using the dosing regimen established in Part I. Blood samples were collected at baseline, one week after each cycle of vaccination, and at follow-up visit for the assessment of NY-ESO-1-specific humoral and cellular immune responses. Results: Enrollment has been completed. 25/26 patients received all 4 vaccinations. The treatment was generally well-tolerated, with no grade 4 adverse events or study-related deaths. The most common toxicities were mild to moderate and included local injection site reactions (granuloma, pruritus, induration) and systemic flu-like symptoms. One patient experienced a grade 3 syncopal episode that was deemed unrelated to the drug. Another patient experienced a grade 3 injection site necrosis that was possibly related to the study drug and was removed from the study prior to receiving the 4th vaccine. Conclusions: This study demonstrates the safety of Resiquimod as an adjuvant for NY-ESO-1 protein vaccination. The study will remain blinded until all immune monitoring assays have been completed. An updated abstract will be submitted once the study is unblinded.

Access State: Open Access

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