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

Study Overview
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Brief Summary
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The purpose of this study is to investigate how effective the study drug IPI-549 is against types of cancers. IPI-549 is considered experimental because it is not approved by the US Food and Drug Administration (FDA) for the treatment of cancer. Patients will be 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.

Detailed Description
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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.

Official Title
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Phase 2 Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer, Head and Neck Carcinoma, Head and Neck Cancer Stage IV, Head and Neck Cancer Stage III, HPV-Related Carcinoma, HPV-Related Malignancy, HPV-Related Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: IPI-549


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: IPI-549 40 mg PO qdaily<br>Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days | Drug: IPI-549<br>* 40mg by mouth (PO) every day (QD) for at least 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PI3K-y changes | To detect IPI-549-induced changes in PI3Kγ-regulated signatures of immune suppression. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Myeloid composition | Compare pre- vs. post-treatment tumor tissue | 2 years | 
| changes in T cell composition | T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression. | 2 years | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | To determine safety and tolerability of IPI-549 and change in tumor size in patients with locally advanced HNSCC | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV positive, HPV negative, HPV-, HPV+, PI3K-γ, microenvironment, immunotherapy, tumor, resection, PI3K, cancer, carcinoma, malignancy, head, neck, throat, esophageal, nasopharyngeal, nasopharynx