Summary

This phase II trial tests how well atezolizumab works in treating patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma that is able to be removed with surgery (resectable). Immunotherapy with atezolizumab, may include changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

Objectives

PRIMARY OBJECTIVES:
I. To determine the safety tolerability of 2 doses of single agent atezolizumab in HPV-driven oropharyngeal squamous cell carcinoma (OPSCC).
II. To determine the pathologic response to 2 doses of single agent atezolizumab in HPV-driven OPSCC.

SECONDARY OBJECTIVES:
I. To evaluate the event free survival at 2 years after treated with this approach followed by pathologic directed adjuvant therapy.

EXPLORATORY EFFICACY OBJECTIVES:
I. The exploratory efficacy objective for this study is to evaluate the efficacy of atezolizumab compared with control (previously studied and published in Nature) on the basis of the following endpoints:
Ia. Determine a biomarker profile of responders versus non-responders to atezolizumab by examining the following biomarkers in the tissue and blood.
Ib. Confirm that PD-1 blockade with atezolizumab will result in an effective proliferation and differentiation PD1+, TCF1+ stem like tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) of patients in HPV-driven OPSCC (correlate these findings with pathologic response).
Ic. Study the temporal differentiation and migration of effector-like cells and their correlation with evidence of pathologic response and tumor immune infiltration.
Id. Correlate these findings with evidence of response using circulating tumor deoxyribonucleic acid (ctDNA) in the peripheral blood.
Ie. Examine the B-cell antigen specific cell (ASC) infiltration and characteristics in the TME of patients and correlate these findings with clinical and pathologic responses.

OUTLINE:
Patients receive atezolizumab intravenously (IV) while on study. Patients undergo computed tomography (CT) scan and magnetic resonance imaging (MRI) throughout the study. Patients may undergo tumor biopsy while on study.

Eligibility

1. The subject is >= 18 years old on the day of consent
2. Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 5 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 5 months after the last dose of study drug(s).
3. Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
4. A male participant must agree to use a contraception as detailed in this protocol during the treatment period and for at least during the active treatment plus an additional 90 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose] after the last dose of study treatment and refrain from donating sperm during this period.
5. The subject has a histologic or cytologic diagnosis of squamous cell carcinoma of the oropharynx, Stage 1 (T1/2 N1) Squamous Cell Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a clinical laboratory improvement act (CLIA) approved laboratory.
6. Patients must not have evidence of extensive or “matted/ fixed” pathologic adenopathy on preoperative imaging.
7. The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT scan as appropriate, within 28 days before the first dose of therapy
8. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
9. Criteria related to comparator drug or background therapy, if applicable: No prior radiation above the clavicles. Patients with a history of a curatively treated malignancy must be disease-free for at least two years prior to entry on study except for carcinoma in situ of cervix, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer
10. Age >= 18 years at time of signing Informed Consent Form
11. Ability to comply with the study protocol
12. Histologically or cytologically confirmed p16+ HPV-driven OPSCC
13. Availability of a representative tumor specimen for exploratory biomarker research
14. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
15. Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1500/GL) without granulocyte colony-stimulating factor support obtained within 14 days prior to initiation of study treatment
16. Lymphocyte count >= 0.5 x 10^9/L (500/GL) obtained within 14 days prior to initiation of study treatment
17. Platelet count >= 100 x 10^9/L (100,000/GL) without transfusion obtained within 14 days prior to initiation of study treatment
18. Hemoglobin >= 90 g/L (9 g/dL) obtained within 14 days prior to initiation of study treatment. * Patients may be transfused to meet this criterion
19. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) =< 2.5 x upper limit of normal (ULN), obtained within 14 days prior to initiation of study treatment with the following exceptions: *Patients with documented liver metastases: AST and ALT =< 5 x ULN *Patients with documented liver or bone metastases: ALP =< 5 x ULN
20. Serum bilirubin =< 1.5 x ULN obtained within 14 days prior to initiation of study treatment with the following exception: *Patients with known Gilbert disease: serum bilirubin =< 3 x ULN
21. Serum creatinine =< 1.5 x ULN obtained within 14 days prior to initiation of study treatment
22. Serum albumin >= 25 g/L (2.5 g/dL) obtained within 14 days prior to initiation of study treatment
23. For patients not receiving therapeutic anticoagulation: international normalization ratio (INR) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN obtained within 14 days prior to initiation of study treatment
24. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
25. Negative human immunodeficiency virus (HIV) test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/uL, and have an undetectable viral load
26. Negative hepatitis B surface antigen (HBsAg) test at screening
27. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test

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