Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

Inclusion Criteria

• Participants must have histologically confirmed adenoid cystic carcinoma with evidence of recurrent or metastatic disease not amenable to potentially curative surgery or radiotherapy.
• Participants must have at least two RECIST v1.1 measurable non-CNS based lesions. Palliative radiation must be indicated for at least one of these lesions, and this lesion must be a candidate for radiation to a dose of 30 Gy of radiation over 5 fractions as deemed by a treating radiation oncologist. Documentation of volume and prescription isodose line will be collected. Re-irradiation of a previously treated lesion is not allowed. One lesion must be in a location where it will not be incorporated into the radiation fields so systemic response can be assessed. However, inclusion of patients with more than 10 measurable lesions is strongly discouraged and all patients must have life expectancy > 6 months.
• Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline and after 2 cycles of pembrolizumab. Participants can be exempt if archival tumor tissue has been collected within 12 months of study enrollment that the Principal Investigator deems it appropriate/sufficient for analysis on this protocol. Biopsy of a lesion outside of the potential radiation treatment field is preferred to maintain consistency across cohorts.
• Participants must have archival tissue from the primary tumor or metastases available for correlative studies. Either a paraffin block or twenty unstained slides are acceptable. If twenty slides are not available, a lesser amount may be acceptable after discussion with the Principal Investigator.
• Prior systemic therapy: At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (4 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤1 (or tolerable grade 2) or back to baseline (except for alopecia or neuropathy). Any number of prior therapies for recurrent/metastatic ACC are allowed, with the exception of previous treatment with PD-1 pathway inhibitors.
• Prior radiation therapy: At least 3 weeks must have elapsed from prior radiation therapy. The prior site of radiotherapy must be documented as reirradiation of the same site is not allowed in this protocol.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A).
• Participants must have documentation of a new or progressive lesion on a radiologic imaging study performed within 12 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 12 months prior to study enrollment. This assessment is performed by the treating investigator. Evidence of progression by RECIST criteria is not required.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.

Table 1 Adequate Organ Function Laboratory Values System Laboratory Value

• Hematological
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Renal
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
• Hepatic
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
• AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin >2.5 mg/dL
• Coagulation
• International Normalized Ratio (INR) or Prothrombin Time (PT)
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X UL