- Patients must be 18 years of age or older.
- Patients with the following histologically confirmed diagnoses will be eligible for
enrolment: p16 positive SCCHN; squamous cell carcinoma of the cervix; p16 positive
squamous cell carcinoma of the vagina or vulva; p16 positive squamous cell carcinoma
of the penis; p16 positive squamous cell carcinoma of the anus or anal canal; EBER
positive NPC; EBER positive Hodgkins and non-hodgkins lymphoma.
- Note: patients with p16 positive SCC of unknown primary origin meeting the minimum
life expectancy and performance status requirements will also be eligible for
enrollment, as the majority of these patients may be assumed to represent
- Patients must be capable of providing consent to enrolment and treatment.
- Patients with a performance status of ECOG 0-1(51) will be eligible for enrolment (see
- Measurable disease must be present according to irRECIST criteria(50).
- Women of child bearing potential (WOCBP) must have a negative serum (or urine)
pregnancy test at the time of screening.
- Patients of childbearing / reproductive potential should use highly effective birth
control methods, as defined by the investigator, during the study treatment period and
for a period of 60 days after the last dose of study drug. A highly effective method
of birth control is defined as those that result in low failure rate (i.e. less than
1% per year) when used consistently and correctly.
- Note: abstinence is acceptable if this is established and preferred contraception for
the patient and is accepted as a local standard.
- Female patients who are breast-feeding should discontinue nursing prior to the first
dose of study treatment and until 120 days after the last dose of study drug.
- Absence of any condition hampering compliance with the study protocol and follow- up
schedule; those conditions should be discussed with the patient before registration in
- The following adequate organ function laboratory values must be met:
- Absolute neutrophil count (ANC) >1.5 x109/L
- Platelet count >100 x109/L
- Hemoglobin >9 g/dL (may have been transfused)
o Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
(or local institutional standard method)
- Total serum bilirubin <1.5x ULN
- AST and ALT <2.5x ULN (or ≤ 5 x ULN for subjects with documented metastatic
disease to the liver)
- Serum albumin > 25 g/L
- International Normalized Ratio (INR) <1.5x ULN (unless patient is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of
intended use of anticoagulants)
- Activated Partial Thromboplastin Time (aPTT) <1.5x ULN (unless patient is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants)
- History of pneumonitis requiring treatment with steroids.
- History of interstitial lung disease.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart
Association Classification Class II), or serious cardiac arrhythmia requiring
- History of another malignancy or a concurrent malignancy;
- Exceptions include patients who have been disease-free for 5 years, or patients with a
history of completely resected non-melanoma skin cancer or successfully treated in
situ carcinoma are eligible, for example cervical cancer in situ.
- Active brain metastases or leptomeningeal disease.
- Patients with treated brain metastases that are stable for 6 weeks will be eligible
- Diagnosis of immunodeficiency.
- Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal,
inhaled, topical steroids, or local steroid injection (e.g., intra-articular
injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone
or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT
- Prior organ transplantation including allogenic stem-cell transplantation.
- Known history of human immunodeficiency virus (HIV).
- Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive
HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid
diseases not requiring immunosuppressive treatment are eligible.
- Patients with hyperthyroidism or hypothyroidism but that are stable on hormone
replacement will not be excluded.
- Active infection requiring systemic therapy.
- Vaccination within 4 weeks of the first dose of Avelumab and while on trials is
prohibited except for administration of inactivated vaccines.
- Patient will not be eligible if the patient is or has an immediate family member
(e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or
sponsor staff directly involved with this trial, unless prospective IRB approval (by
chair or designee) is given allowing exception to this criterion for a specific
- Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however,
alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety
risk based on investigator's judgment are acceptable.
- Known prior severe hypersensitivity to investigational product or any component in its
formulations, including known severe hypersensitivity reactions to monoclonal
antibodies (NCI CTCAE v4.03 Grade ≥ 3).
- Other severe acute or chronic medical conditions including immune colitis,
inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric
conditions including recent (within the past year) or active suicidal ideation or
behavior; or laboratory abnormalities that may increase the risk associated with study
participation or study treatment administration or may interfere with the
interpretation of study results and, in the judgment of the investigator, would make
the patient inappropriate for entry into this study.