| Eligibility |
Inclusion Criteria:
- Participants with biopsy proven, surgically resectable head and neck cutaneous
squamous cell carcinoma regionally metastatic to lymph nodes in the head and/or neck
with a historical or unknown (but not concurrent) primary site
- Patients must be >= 18 years
- Patients with resectable regionally metastatic HNCSCC from an unknown or historical
primary and no evidence of distant metastatic disease
- Full decision-making capacity and consent provided and documented
- Radiographically measurable disease per immune Response Evaluation Criteria in Solid
Tumors (iRECIST)
- Surgically resectable disease per standard of care (SoC)
- For Women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods as defined below: * Women must
remain abstinent or use contraceptive methods with a failure rate of < 1% per year
during the treatment period and for 5 months after the final dose of atezolizumab * A
woman is considered to be of childbearing potential if she is postmenarchal, has not
reached a postmenopausal state (>= 12 continuous months of amenorrhea with no
identified cause other than menopause), and has not undergone surgical sterilization
(removal of ovaries and/or uterus). The definition of childbearing potential may be
adapted for alignment with local guidelines or requirements * Examples of
contraceptive methods with a failure rate of < 1% per year include bilateral tubal
ligation, male sterilization, hormonal contraceptives that inhibit ovulation,
hormone-releasing intrauterine devices, and copper intrauterine devices * The
reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical trial and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not adequate methods of contraception
- Men: abstinent or using effective contraception method
- Tumor tissue sample adequate for PD-L1 and biomarker studies
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Availability of a representative tumor specimen for exploratory biomarker research
- Life expectancy >= 2 years
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1500/uL) without granulocyte
colony-stimulating factor support (within 14 days prior to initiation of study
treatment)
- Lymphocyte count >= 0.5 x 10^9/L (500/uL) (within 14 days prior to initiation of study
treatment)
- Platelet count >= 50 x 10^9/L (50,000/uL) without transfusion (within 14 days prior to
initiation of study treatment)
- Hemoglobin >= 80 g/L (8 g/dL) (within 14 days prior to initiation of study treatment)
* Patients may be transfused to meet this criterion
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
phosphatase (ALP) =< 2.5 x upper limit of normal (ULN) (within 14 days prior to
initiation of study treatment)
- Serum bilirubin =< 1.5 x ULN (within 14 days prior to initiation of study treatment)
with the following exception: * Patients with known Gilbert disease: serum bilirubin
=< 3 x ULN
- Serum creatinine =< 1.5 x ULN or creatinine clearance >= 60 mL/min (calculated using
the Cockcroft-Gault formula (within 14 days prior to initiation of study treatment)
- Serum albumin >= 25 g/L (2.5 g/dL) (within 14 days prior to initiation of study
treatment)
- For patients not receiving therapeutic anticoagulation: international normalized ratio
(INR) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- 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, and have an
undetectable viral load
- Negative hepatitis B surface antigen (HBsAg) test at screening
- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total
HBcAb test followed by a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA)
test at screening
- The HBV DNA test will be performed only for patients who have a negative HBsAg test
and a positive total HBcAb test
Exclusion Criteria:
- Distant metastatic disease
- Unresectable disease: As defined by: common or internal carotid artery encasement or
involvement of the skull base involvement or pre-vertebral fascia
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently) * Patients with indwelling
catheters (e.g., PleurX) are allowed
- Uncontrolled (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum
calcium > ULN) or symptomatic hypercalcemia
- Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome,
or multiple sclerosis, with the following exceptions: * Patients with a history of
autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible
for the study * Patients with controlled type 1 diabetes mellitus who are on an
insulin regimen are eligible for the study * Patients with eczema, psoriasis, lichen
simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients
with psoriatic arthritis are excluded) are eligible for the study provided all of
following conditions are met: ** Rash must cover < 10% of body surface area ** Disease
is well controlled at baseline and requires only low-potency topical corticosteroids
** No occurrence of acute exacerbations of the underlying condition requiring psoralen
plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral
calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12
months * Any history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g.,
bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or
evidence of active pneumonitis on screening chest computed tomography (CT) scan.
History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Known active tuberculosis
- Significant cardiovascular disease (such as New York Heart Association class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3
months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation
of study treatment, or anticipation of need for a major surgical procedure during the
study
- History of malignancy within 2 years prior to screening, with the exception of
malignancies with a negligible risk of metastasis or death (e.g., 5-year overall
survival [OS] rate > 90%), such as adequately treated carcinoma in situ of the cervix,
non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or
stage I uterine cancer
- Severe infection within 4 weeks prior to initiation of study treatment, including, but
not limited to, hospitalization for complications of infection, bacteremia, or severe
pneumonia. Severe infection is defined as that requiring inpatient treatment of
hospitalization
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment * Patients receiving prophylactic antibiotics (e.g., to prevent a
urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
eligible for the study
- Prior allogeneic stem cell or solid organ transplantation
- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may affect
the interpretation of the results, or may render the patient at high risk from
treatment complications
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
treatment, or anticipation of need for such a vaccine during atezolizumab treatment or
within 6 months after the final dose of atezolizumab
- Current treatment with anti-viral therapy for HBV. Patient on suppressive therapy
should excluded
- Treatment with investigational therapy within 28 days prior to initiation of study
treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug
(whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNF-alpha agents) within 2 weeks prior to initiation of study treatment, or
anticipation of need for systemic immunosuppressive medication during study treatment,
with the following exceptions: * Patients who received acute, low-dose (defined as <
200 mg / day hydrocortisone or equivalent) corticosteroid treatment (e.g., 48 hours of
corticosteroids for a contrast allergy) are eligible for the study after principal
investigator confirmation has been obtained * Patients who received mineralocorticoids
(e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease
(COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal
insufficiency are eligible for the study
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
or fusion proteins
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation
- Concurrent identifiable primary cutaneous head and neck squamous cell carcinoma tumor
- Pregnant or breastfeeding, or intention of becoming pregnant during study treatment or
within 5 months after the final dose of study treatment
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