In Situ Autovaccination against Solid Cancers with Intratumoral Hiltonol Poly ICLC A phase II Adaptive Multicenter Clinical Study

DESCRIPTION provided by applicant Hiltonol poly ICLC is a stabilized dsRNA therapeutic viral mimic or andapos danger signalandapos that activates multiple elements of innate and adaptive immunity It is a standalone immunomodulator but when properly combined with antigen it generates a comprehensive Th weighted immune response best suited for antiviral and antitumor action This project will combine Hiltonol with cancer patientsandapos own tumor antigens in situ to generate a comprehensive systemic immune response against the tumor and its metastases Objectives To determine the safety of intratumoral IT Poly ICLC To explore efficacy as manifested by irRC defined disease control and progression free survival at weeks Secondary objectives are overall survival and immunologic response in blood and tumor biopsy including immunoscore Indications Tumor groups Unresectable stage b c or IV M a or M b melanomas that are accessible to IT injections Unresectable head and neck cancers that are accessible to IT injections Sarcomas that are accessible to IT injections Squamous cell carcinoma of the skin accessible to IT injections Study Design A two stage adaptive design Phase II clinical study with a pilot segment and an extension segment for the single tumor type showing the best clinical responses in the pilot phase Pilot SBIR phase I segment Ten volunteer patients will be treated per group for a total of patients in the initil pilot phase of the study Treatment consists of two cycles of intratumoral IT Hiltonol priming plus intramuscular IM Hiltonol maintenance One accessible tumor site will be targeted for initial IT injections of poly ICLC thrice weekly for weeks followed by IM maintenance twice weekly for six weeks in each cycle A second cycle will be followed by a week no treatment rest period to allow for evaluation of tumor response at week in the absence of inflammation Extension SBIR phase II segment Based on the safety and clinical response for patients in each tumor group during the pilot phase of the study one of the groups showing IRRC defined stabilization or regression of disease at weeks in at least two of the initial ten patiets will be selected for further study under this proposal Appropriate indication specific statistics will be applied and an estimated additional patients will be accrued to that group for an estimated total of patients in that group Accrual targets may be further modified depending on the extent of response other data collected and results of a planned industry meeting with FDA Survival and PFS will be estimated using Kaplan Meir curves PUBLIC HEALTH RELEVANCE The host targeted personalized in situ auto vaccination strategy proposed here uses Hiltonol to generate a comprehensive Th weighted immune response to the patientandapos s own tumor associated antigens and it may thus be applicable to a variety of histologic tumor types The total US incidence of the tumor types in this proposal is about range with upwards of deaths yearly Development of an effective simple and inexpensive treatment with intratumoral IT poly ICLC Hiltonol R for any of these tumor types would have major societal as well as commercial significance