Spots Global Cancer Trial Database for Afatinib and Nivolumab as Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Study Description

Brief Summary: This phase I/Ib trial will assess the dose, safety and side effects of the combination of the cancer drugs afatinib (GILOTRIF®) and nivolumab (OPDIVO®) and to assess the anti-cancer effects of this combination of drugs when used to treat patients with advanced head and neck cancers that did not respond to previous treatments.

Detailed Description: Primary Objectives: Phase I: To determine dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of afatinib when given in combination with nivolumab for subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy Phase IB: To determine long term safety of afatinib in combination with nivolumab when administered to subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck who had experienced disease progression during or after platinum- and cetuximab-based chemotherapy regimen. Secondary Objectives: To assess progression free survival and overall survival of afatinib in combination with nivolumab when given to subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy. To estimate HPV stratified ORR as assessed by irRECIST in recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy. Exploratory Objectives: * Determination of key molecular alterations that may confer treatment resistance. Specifically, we will examine key somatic mutations in ERBB1 (exons 18-21), ERBB2 (exon 20), and BRAF (V600) genes. We will further characterize the expression levels of ErbB2 and phosphatase and tensin homolog (PTEN) in tumor samples. * Characterization of active CD8+ T-cell density and PD-L1 expression levels in the tumor parenchyma pre- and on-treatment. Immunogenicity will be assessed by expression and localization of key molecules PD-1, PD-L1, CTLA-4, TIM-3, LAG-3 and OX40 within the tumor parenchyma. * Characterization of circulating monocytic myeloid-derived suppressor cells (m-MDSCs) frequency from pre-treatment peripheral blood samples. * Characterization of HBD3 expression in the tumor parenchyma from pre-treatment tumor tissue samples.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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