| Eligibility |
Inclusion Criteria:
- Cohort 1 only: Patients must have pathologically or cytologically confirmed adenoid
cystic carcinoma. Cancers arising from non-salivary gland primary sites are allowed.
- Patients must have pathologically or cytologically confirmed salivary gland cancer of
any histology except for adenoid cystic carcinoma.
- Patients must have recurrent and/or metastatic disease not amenable to potentially
curative surgery or radiotherapy.
- At least 2 weeks must have elapsed since the end of prior systemic treatment and/or 4
weeks since completion of radiotherapy with resolution of all treatment-related
toxicity to NCI CTCAE Version 4.0 grade =1 (or tolerable grade 2) or back to baseline
(except for alopecia, lymphopenia, or hypothyroidism) prior to starting study drug
treatment. Any number of prior therapies for recurrent/metastatic salivary gland
cancer are allowed.
NOTE: Patients previously treated with hormonal therapies (e.g., drugs targeting the
androgen receptor) may continue these drugs prior to trials enrollment and concomitantly
with study therapy.
- Patients must have RECIST v1.1 measurable disease.
- Cohort 1 and acinic cell carcinoma patients in Cohort 2 only: Patients must have
documentation of a new or progressive lesion on a radiologic imaging study performed
within 6 months prior to study enrollment (progression of disease over any interval is
allowed) and/or new/worsening disease related symptoms within 6 months prior to study
enrollment. Note: This assessment will be performed by the treating investigator.
Evidence of progression by RECIST criteria is not required.
- Age = 18 years.
- ECOG performance status 0 or 1 (or Karnofsky = 70%).
- Patients must have tissue from the primary tumor or metastases available for
correlative studies. Either a paraffin block or at least 20 unstained slides are
acceptable (30 unstained slides would be ideal). (If less than twenty unstained slides
are available and a paraffin bloc is not available, the patient may be able to
participate at the discretion of the investigator.)
- Patients must agree to undergo two research biopsies of malignant lesions. Tumor
tissue obtained prior to study consent or treatment as part of standard of care can
also be submitted in lieu of performance of the first pre-treatment biopsy, if the
Principal Investigator deems it to be of sufficient quantity/quality/timeliness.
Patients may be exempt from biopsy if 1) the investigator or person performing the
biopsy judges that no tumor is accessible for biopsy, 2) the investigator or person
performing the biopsy feels that the biopsy poses too great of a risk to the patient,
or 3) the patient's platelet count is <100,000/mcl or he/she cannot be safely removed
from anti-coagulation therapy (if the anti-coagulation therapy needs to be temporarily
held for the biopsy procedure). If the only tumor accessible for biopsy is also the
only lesion that can be used for RECIST v1.1 response evaluation, then the patient may
be exempt from biopsy. If the investigator deems a second research biopsy to be high
risk after a patient has completed the first research biopsy, the patient may be
exempt from the second biopsy.
- Screening laboratory values must meet the following criteria:
- WBC = 2000/µL
- Neutrophils = 1500/µL
- Platelets = 100 x10^3/µL
- Hemoglobin > 9.0 g/dL
- AST/ALT = 3 x ULN
- Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have
total bilirubin < 3.0 mg/dL)
- Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min (if using
the Cockcroft-Gault formula below):
Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
- Women of childbearing potential (WOCBP)* must use appropriate method(s) of
contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30
days plus the time required for nivolumab to undergo five half-lives) after the last
dose of investigational drug.
- WOCBP is defined as any female who has experienced menarche and who has not
undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who
is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea
in a woman over 45 in the absence of other biological or physiological causes.
Women who are not of childbearing potential are not required to use contraception.
- Women of childbearing potential must have a negative serum or urine pregnancy test
upon study entry.
- Men who are sexually active with women of child bearing potential must use adequate
contraception upon study entry until 31 weeks after the last dose of study treatment.
Men who are surgically sterile or azoospermic do not require contraception.
Exclusion Criteria:
- Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or treated
metastatic brain or leptomeningeal tumors are allowed).
- Current or prior use of immunosuppressive doses of systemic corticosteroids (>10
mg/day prednisone equivalents) or other immunosuppressive medications within 2 weeks
of study drug administration. NOTE: Subjects are permitted to use topical, ocular,
intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic
absorption). Physiologic replacement doses of systemic corticosteroids are permitted,
even if >10 mg/day prednisone equivalents. A brief course of corticosteroids for
prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions
(eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- Active, known, or suspected autoimmune disease within the past 2 years. NOTE: Subjects
are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual
hypothyroidism due to autoimmune condition only requiring hormone replacement,
psoriasis not requiring systemic treatment, or conditions not expected to recur in the
absence of an external trigger
- Patients should be excluded if they have had prior systemic treatment with an
anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell costimulation or immune checkpoint pathways.
- Patients should be excluded if they have a known history of testing positive for
hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus antibody (HCV
antibody) indicating acute or chronic infection (those with treated hepatitis B or C
infection and a negative viral load prior to study entry would be eligible)
- Patients should be excluded if they have a known history of testing positive for human
immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- History of allergy to study drug components.
- History of severe hypersensitivity reaction to any monoclonal antibody.
- Women who are pregnant or breast-feeding.
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