Curebiotech, Inc., FOA # PA-21-262 Application number 1121483 Head and neck squamous cell carcinoma (HNSCC) is the seventh leading cause of cancer-relatedmortality in the world. Radiation therapy (RT) is routinely used for patients with locoregionally advanceddisease. The historical 5-year overall survival rates for locally advanced HNSCC after treatment with surgery,chemotherapy, and RT is ~50%. Many of these patients relapse after initial therapy and/or develop metastaticdisease, and the prognosis for these patients remains poor, with a median survival between 6 to 12 months.Immunotherapy with anti-PD-1 antibodies yields a response rate less than 20%. Hence, there is a pressingclinical need to develop alternative approaches for patients with relapsed and/or metastatic HNSCC.CureBiotech Inc. is a preclinical stage biotech company that focuses on toll-like receptor 7/8 agonist,resiquimod. Resiquimod is more potent and has better bioavailability than imiquimod, an FDA approvedimmune modulating drug. CureBiotech has developed an innovative intratumoral controlled release formulationof resiquimod, CB101, which sequesters the drug to a local site using a polymer matrix, with the aim ofavoiding systemic adverse immune response. It showed superior treatment efficacy over unformulatedresiquimod in multiple preclinical models. Locally advanced or relapsed HNSCC is easily accessible forintratumoral injection of CB101. We postulate that CB101 will significantly augment the response of cancers toRT via modulating the tumor microenvironment (TME). In Aim 1, we will optimize dose and treatment scheduleof CB101 and RT in HNSCC pre-clinical models. Since RT may increase PD-L1 expression on tumor cells, inAim 2, we will investigate the treatment efficacy of anti-PD-1 antibodies with CB101/RT combination. Weexpect that lower doses of RT with CB101 may yield the same or better results as higher dose radiation alonebut with reduced toxicity, making RT resistant tumors sensitive and enhancing the abscopal effect of RT.Successful completion of these aims will have a direct impact on the design of future clinical trials. We havethe scientific and personnel capability to achieve these aims quickly and meticulously. The data generated inthis project will be included in an IND application of a phase I clinical trial of CB101/RT in HNSCC patients tothe FDA.
Public Health Relevance Statement: Curebiotech, Inc., FOA # PA-21-262 Application number 1121483
PROJECT NARRATIVE
Relapsed head and neck squamous cell carcinoma has poor prognosis and few treatment options are
available to these patients. CureBiotech Inc is developing a new immune modulating compound, CB101, to be
combined with radiation therapy to treat this disease. It is expected that lower doses of radiation therapy with
CB101 may yield the same or better results as higher dose radiation alone but with reduced toxicity, making
radiation therapy-resistant tumors sensitive and enhancing the abscopal effect of radiation therapy.
Project Terms: 