Poly-ICLC (Hiltonol) and Anti-PD1 or Anti-PD-L1

Inclusion Criteria

1. Histologically confirmed diagnosis of Solid Cancer, independent of PD-L1 tumor status.
2. Patients must be 18 years of age or older.
3. Unresectable disease. Patients with resectable disease but who refuse surgery may be enrolled after a documented consultation with a surgeon.
4. Radiologically or visually measurable disease that is at least 10mm in longest dimension, AND/OR with elevated disease specific serum markers that can be followed for progression (eg CA-125, AFP, PSA, CA19-9 or CEA)
5. ECOG performance status of ≤ 2.
6. Acceptable hematologic, renal and liver function as follows:

   A) Absolute neutrophil count \> 1000/mm3 B) Platelets \> 50,000/mm3, C) Creatinine ≤ 2.5 mg/dl, D) Total bilirubin ≤ 1.5 mg/dl, unless due to tumor or Gilbert's syndrome E) Transaminases ≤ 2 times above the upper limits of the institutional normal. F) INR\<2 if off of anticoagulation. Patients on anticoagulation therapy with an INR\>2 may be enrolled at the discretion of the investigator if they have not had any episodes of severe hemorrhage.
7. Patients must be able to provide informed consent.
8. Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Contraception must be continued for at least 2 months following the last dose of Poly-ICLC. Women of childbearing potential must have a negative pregnancy test. While animal reproductive studies have been negative, the simulated viral infection and anti-proliferative activity of this experimental drug may theoretically affect the developing fetus or nursing infant.

   Cohort Specific Inclusion Criteria (see § 9.5 Evaluation of Best Overall Response (BOR)

   Cohort A
9. Patients who have received at least 8 weeks of immunotherapy.
10. Patients have progressive disease based on RECIST 1.1 criteria

    Cohort B)
11. Patients who have received at least 8 weeks of aPD1 or aPDL1 immunotherapy.
12. Patients have stable disease or a partial response based on RECIST 1.1 criteria.

    Cohort C)
13. Patients who have not received an anti-PD-1 or anti-PD-L1 agent, but who carry a diagnosis for which one of these agents is the SOC.
14. Patients willing to delay receipt of first dose of anti-PD-1 or anti-PD-L1 until after the receipt of their first two doses of intramuscular Poly-ICLC

Exclusion Criteria

1. Patients may not be receiving any other investigational agents.
2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
3. Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
4. Has a diagnosis of primary 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.
5. 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 acceptable.
6. 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.
7. HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with \<200 CD4+ T cells/microliter in the peripheral blood.
8. Has known active Hepatitis B (e.g., HBV detected by elevated PCR or active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
9. History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
10. Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps)
11. Principal investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient.