NCT03652233

Afatinib and Nivolumab as Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Afatinib and Nivolumab for Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Not Previously Treated With Immunotherapy.

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Recurrent Squamous Cell Carcinoma of the Head or Neck
• Metastatic Squamous Cell Carcinoma of the Head or Neck
• Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Nivolumab	Given by vein every 14 days for up to 12 months
DRUG	Afatinib	Taken by mouth daily for up to 12 months

Timeline

• Start date: 2018-11-02
• Primary completion: 2021-11-01
• Completion: 2022-11-01
• First posted: 2018-08-29
• Last updated: 2019-06-20

Regulatory

• FDA-regulated drug study