IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

This is a phase 2 window of opportunity trial in patients with locally advanced head and neck cancer. A key objective is to provide the first proof that macrophage phenotype switching can be accomplished in humans and lay the groundwork for future trials of this novel approach to immune therapy. Patients who are candidates for surgical resection will be enrolled and treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

The study team hypothesizes that mRNA signatures of immune response will be increased in IPI-549-treated patients. For the efficacy endpoints, RECISTv1.1 will be used.

Inclusion criteria

• Have locally advanced that is amenable to surgical resection
• Must be able to swallow tablets
• Must be able to undergo a core tumor biopsy.
• Must have adequate organ function.

Exclusion criteria

• Diagnosis of cutaneous squamous cell carcinoma (SCC) or Epstein-Barr virus (EBV) related nasopharynx cancer.
• Planned major surgery within 4 weeks prior to initiation of study drug
• Patients treated with chemotherapy, biologic therapy, or other investigational agent within < 28 days of starting study drug
• History of infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus (HCV)
• On going treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids
• Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g. gastric bypass surgery, gastrectomy)
• Female subjects who are pregnant or breastfeeding
• Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or prostate intraepithelial neoplasia