Vaccination With Flt3L, Radiation, and Poly-ICLC

• Have pathologically confirmed iNHL, MBC or HNSCC
• Lymphoma subtypes that may be enrolled include small lymphocytic lymphoma

Exclusion Criteria:

• Is currently participating and receiving an investigational therapy (not standard therapies) or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment.
• Any patients that require immediate treatment or cytoreduction are excluded. Note: This is applicable for iNHL, MBC, and HNSCC populations.
• Any patient with transformed lymphoma, or patients with grade 3A follicular lymphoma are excluded.
• MZL patients with gastric MALT lymphomas with disease localized to the stomach are excluded, and any patient with disease in a site where injection is determined to be high risk.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
• Hypersensitivity to pembrolizumab, poly-ICLC, Flt3L or any of their excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to study D22 (First dose of pembrolizumab) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to agents administered more than 28 days before initiation of in situ vaccine protocol.
• Has had prior chemotherapy, targeted small molecule therapy, or RT therapy within 14 days prior to study D0 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to a previously administered agent. Note: Patients with chronic ≤ Grade 2 AEs such as neuropathy are an exception to this criterion and may qualify for the study.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has known active central nervous system metastases, leptomeningeal disease and/or lymphomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include leptomeningeal disease or lymphomatous meningitis, which are excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a systemic treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy at time of enrollment in trial.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical or anal cancer, prostate cancer on stable dose of hormonal therapy without rising PSA.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• Has known psychiatric or substance abuse disorders that investigator believes would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment (roughly two and a half years after enrollment).
• HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen.
• Has known active Hepatitis B (e.g., HBV detected by PCR) or active Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Patients with grade 3B follicular lymphoma